BioPAX pathway converted from "Regulation of NF-kappa B signaling" in the Reactome database. Regulation of NF-kappa B signaling This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> LEFT-TO-RIGHT LRRC14 binds IKBKB and CHUK LRRC14 binds IKBKB and IKBKA This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> CHUK G3V926 Reactome DB_ID: 9947389 cytosol GENE ONTOLOGY GO:0005829 UniProt:G3V926 Rattus norvegicus NCBI Taxonomy 10116 UniProt G3V926 1 EQUAL 745 EQUAL Reactome Database ID Release 82 9947389 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9947389 Reactome R-RNO-168104 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-168104.1 Reactome http://www.reactome.org Lrrc14 LRRC14 Q569B5 Reactome DB_ID: 10033626 UniProt:Q569B5 Lrrc14 UniProt Q569B5 1 EQUAL 493 EQUAL Reactome Database ID Release 82 10033626 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033626 Reactome R-RNO-9749455 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9749455.1 IKBKB Q9QY78 Reactome DB_ID: 9946542 UniProt:Q9QY78 UniProt Q9QY78 1 EQUAL 756 EQUAL Reactome Database ID Release 82 9946542 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9946542 Reactome R-RNO-168114 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-168114.1 CHUK:IKBKB:LRRC14 Reactome DB_ID: 10033628 1 1 1 Reactome Database ID Release 82 10033628 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033628 Reactome R-RNO-9749467 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9749467.1 Reactome Database ID Release 82 10033630 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033630 Reactome R-RNO-9749505 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9749505.1 GENE ONTOLOGY GO:0043124 gene ontology term for cellular process MI MI:0359 Leucine-rich repeat-containing protein 14 (LRRC14) binds to the helix-loop-helix (HLH) domain of IKBKB (Wu C et al. 2016). This binding blocks IKBKB interaction with IKBKG (NEMO) disrupting IκB kinase (IKK) complex formation and NF-kappa-B activation (Wu C et al. 2016). 27426725 Pubmed 2016 LRRC14 attenuates Toll-like receptor-mediated NF-κB signaling through disruption of IKK complex Wu, Chenglei Yang, Yexin Ou, Jiayu Zhu, Liang Zhao, W Cui, Jun Exp Cell Res 347:65-73 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT NLRX1 binds CHUK:IKBKB:IKBKG NLRX1 binds activated IKK complex This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Q5FVQ8 K63polyUb-NLRX1 Reactome DB_ID: 10033618 UniProt:Q5FVQ8 UniProt Q5FVQ8 ubiquitinylated lysine MOD MOD:01148 87 EQUAL 975 EQUAL Reactome Database ID Release 82 10033618 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033618 Reactome R-RNO-9749510 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9749510.1 CHUK:IKBKB:IKBKG Reactome DB_ID: 9949690 1 1 IKBKG Q6TMG5 Reactome DB_ID: 9942503 UniProt:Q6TMG5 UniProt Q6TMG5 1 EQUAL 419 EQUAL Reactome Database ID Release 82 9942503 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9942503 Reactome R-RNO-168108 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-168108.1 1 Reactome Database ID Release 82 9949690 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9949690 Reactome R-RNO-168113 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-168113.1 CHUK:IKBKB:IKBKG:K63polyUb-NLRX1 Reactome DB_ID: 10033620 1 1 Reactome Database ID Release 82 10033620 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033620 Reactome R-RNO-9749472 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9749472.1 Reactome Database ID Release 82 10033622 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033622 Reactome R-RNO-9749471 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9749471.1 Nucleotide binding oligomerization domain (NOD)-like receptor (NLR) family member X1 (NLRX1) has been implicated in regulation of the Toll-like receptor (TLR)-mediated nuclear factor kappa-B (NF-kappa-B) signaling pathway. NLRX1 deficiency enhanced phosphorylation of catalytic subunits (CHUK and IKBKB) of the IkB kinase (IKK) complex and NF-kappa-B activation and led to elevated production of inflammatory cytokines in mouse cells in response to bacterial lipopolysaccharide (LPS, a TLR4 ligand) (Allen IC et al. 2011; Xia X et al. 2011; Ma D et al. 2019). NLRX1-knockdown mice showed enhanced susceptibility to LPS-induced septic shock thus further confirming that NLRX1 functions as a negative regulator of TLR signaling in vivo (Xia X et al. 2011). NLRX1 was shown to interact with TRAF6 (Allen et al. 2011; Xia X et al. 2011) and the IKK complex (CHUK:IKBKB:IKBKG) (Xia X et al. 2011) in human and mouse cells. Specifically, in unstimulated cells, NLRX1 was shown to associate with TRAF6 (Xia X et al. 2011). Upon stimulation with LPS, NLRX1 is thought to undergo K63-linked polyubiquitination. Although TRAF6 possesses E3 ubiquitin ligase activity, the TRAF6 deficiency did not affect NLRX1 ubiquitination in mouse embryonic fibroblast (MEF) (Xia X et al. 2011). Further studies are required to identify E3 ubiquitin ligase which is responsible for the ubiquitination of NLRX1. Ubiquitinated NLRX1 then binds to the IKK complex, blocking phosphorylation of the catalytic subunits CHUK (IKBKA) and IKBKB (Xia X et al. 2011). Mutagenesis studies showed that the C-terminal leucine-rich repeat (LRR) domain of NLRX1 binds to the kinase domain of IKBKB (Xia X et al. 2011). <p>The regulatory effects of NLRX1 are highly cell type specific (reviewed in Fekete T et al. 2021). As a regulator of inflammation, NLRX1 has been implicated in the pathology of diverse diseases (reviewed in Pickering RJ & Booty LM 2021).<p>This Reactome event shows interaction between NLRX1 and the IKK complex. 30861394 Pubmed 2019 NLRX1 alleviates lipopolysaccharide-induced apoptosis and inflammation in chondrocytes by suppressing the activation of NF-κB signaling Ma, Ding Zhao, Yangxue She, Jiang Zhu, Yandong Zhao, Y Liu, Liang Zhang, Yingang Int Immunopharmacol 71:7-13 33525671 Pubmed 2021 Focusing on the Cell Type Specific Regulatory Actions of NLRX1 Fekete, Tünde Bencze, Dóra Bíró, Eduárd Benko, Szilvia Pázmándi, Kitti Int J Mol Sci 22: 21703539 Pubmed 2011 NLRX1 negatively regulates TLR-induced NF-κB signaling by targeting TRAF6 and IKK Xia, Xiaojun Cui, Jun Wang, Helen Y Zhu, Liang Matsueda, Satoko Wang, Qinfu Yang, Xiaoang Hong, Jun Songyang, Z Chen, Zhijian J Wang, Rong-Fu Immunity 34:843-53 33314068 Pubmed 2021 NLR in eXile: Emerging roles of NLRX1 in immunity and human disease Pickering, Robert J Booty, Lee M Immunology 162:268-280 21703540 Pubmed 2011 NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-κB signaling pathways Allen, Irving C Moore, Chris B Schneider, Monika Lei, Yu Davis, Beckley K Scull, Margaret A Gris, Denis Roney, Kelly E Zimmermann, Albert G Bowzard, John B Ranjan, Priya Monroe, Kathryn M Pickles, Raymond J Sambhara, Suryaprakash Ting, Jenny P Y Immunity 34:854-65 LEFT-TO-RIGHT NLRC5 binds IKBKB and CHUK NLRC5 binds IKBKB and IKBKA This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Nlrc5 NLRC5 M0R4M1 Reactome DB_ID: 10033668 UniProt:M0R4M1 Nlrc5 UniProt M0R4M1 1 EQUAL 1866 EQUAL Reactome Database ID Release 82 10033668 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033668 Reactome R-RNO-937324 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-937324.1 CHUK:IKBKB:NLRC5 Reactome DB_ID: 10033670 endoplasmic reticulum membrane GENE ONTOLOGY GO:0005789 1 1 1 Reactome Database ID Release 82 10033670 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033670 Reactome R-RNO-9750228 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9750228.1 Reactome Database ID Release 82 10033675 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033675 Reactome R-RNO-9750226 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9750226.1 The I-kappa-B-kinase (IKK) complex, a key regulator of the nuclear factor kappa B (NF-kB) signaling pathway, consists of two catalytic subunits, IKBKA (KKα or CHUK) and IKBKB (IKKβ), associated with a regulatory subunit IKBKG (NEMO). The IKK complex is responsible for the phosphorylation of inhibitors of NF-kB (IkBs), such as NFKBIA or NFKBIB. Once phosphorylated, IkB undergoes ubiquitin-mediated degradation, releasing the transcription factor NF-kB thereby allowing translocation of NF-kB to the nucleus to regulate gene expression (Oeckinghaus A and Ghosh S 2009). NOD-like receptor C5 (NLRC5), the transcriptional activator of genes coding for MHC-I, has been implicated in the regulation of inflammatory pathways and IFN-dependent antiviral defense (Benko S et al. 2010; Cui J et al. 2010). Overexpression of NLRC5 inhibited NFkB-luciferase reporter activity in human embryonic kidney 293T (HEK293T) cells treated with interleukin (IL)-1β, TNF-α or toll-like receptor (TLR) agonists such as bacterial LPS (TLR4 ligand) or R848 (TLR7/8 ligand) (Cui J et al. 2010). Similar findings were obtained with human monocytic THP-1 cells and murine embryonic fibroblasts (MEFs) (Cui J et al. 2010). Further, NLRC5 deficiency resulted in enhanced phosphorylation of IKBKB, CHUK, and increased expression of NF-kB-responsive cytokines (such as TNF-α and IL-6), in LPS-stimulated THP-1 and mouse macrophage RAW264.7 cells (Cui J et al. 2010). NLRC5 deficiency enhanced NF‐kB activation in mouse cells in response to TLR3, TLR4, TLR7, TLR9 ligands (Tong Y et al. 2012) and TLR2 ligand (Wang M et al. 2019). Knockdown of NLRC5 also enhanced cytokine response and antiviral immunity in vesicular stomatitis virus (VSV)-treated primary human monocytes, primary murine macrophages and RAW264.7 cells. Studies with NLRC5-deficient mice confirmed the regulatory role of NLRC5 in the induction of NF-kB and type I interferon in response to LPS or VSV infection (Tong Y et al. 2012). Moreover, NLRC5 co-immunoprecipitated with IKBKA (CHUK) and IKBKB subunits, but not with IKBKG, upon co-expression of tagged proteins in HEK293T cells (Cui J et al. 2010). Mutagenesis analysis revealed that human NLRC5 targets the amino-terminal kinase domain (KD) of IKBKB. Fractionation of RAW264.7 cells extracts on a size-exclusion column followed by immunoblotting analysis showed that both CHUK:IKBKB:IKBKG and CHUK:IKBKB:NLRC5 complexes co-exist in unstimulated cells suggesting that NLRC5 inhibits the interaction between IKBKG (NEMO) and IKBKB/CHUK (Cui J et al. 2010). The dynamics of NLRC5 interaction with IKBKB/CHUK upon stimulation is regulated by TRAF2/TRAF6-dependent ubiquitination of NLRC5 (Meng Q et al. 2015). These data suggest that NLRC5 negatively regulates NF-kappa-B activation via targeting IKBKB and CHUK. 20610642 Pubmed 2010 NLRC5 limits the activation of inflammatory pathways Benko, Szilvia Magalhaes, Joao G Philpott, Dana J Girardin, Stephen E J Immunol 185:1681-91 22473004 Pubmed 2012 Enhanced TLR-induced NF-κB signaling and type I interferon responses in NLRC5 deficient mice Tong, Yanzheng Cui, Jun Li, Qingtian Zou, Jia Wang, Helen Y Wang, Rong-Fu Cell Res 22:822-35 26620909 Pubmed 2015 Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch Meng, Qingcai Cai, Chunmei Sun, Tingzhe Wang, Qianliang Xie, Weihong Wang, Rongfu Cui, Jun J Cell Biol 211:1025-40 20066092 Pubmed 2009 The NF-kappaB family of transcription factors and its regulation Oeckinghaus, Andrea Ghosh, Sankar Cold Spring Harb Perspect Biol 1:a000034 20434986 Pubmed 2010 NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways Cui, J Zhu, Lijun Xia, X Wang, HY Legras, X Hong, J Ji, J Shen, P Zheng, S Chen, ZJ Wang, RF Cell 141:483-96 30945291 Pubmed 2019 NLRC5 negatively regulates LTA-induced inflammation via TLR2/NF-κB and participates in TLR2-mediated allergic airway inflammation Wang, Muzi Wang, Lixia Fang, Lei Li, Shuai Liu, Rongyu J Cell Physiol 234:19990-20001 INHIBITION Reactome Database ID Release 82 10033676 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033676 Nlrc5 K63polyUb-NLRC5 M0R4M1 Reactome DB_ID: 10033673 1178 EQUAL 87 EQUAL 975 EQUAL Reactome Database ID Release 82 10033673 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033673 Reactome R-RNO-9750938 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9750938.1 ACTIVATION Reactome Database ID Release 82 10033677 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033677 Usp14 USP14 Q5U2N2 Reactome DB_ID: 10004973 UniProt:Q5U2N2 Usp14 UniProt Q5U2N2 1 EQUAL 494 EQUAL Reactome Database ID Release 82 10004973 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10004973 Reactome R-RNO-5689541 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-5689541.1 LEFT-TO-RIGHT 6.3.2.19 TRAF2,6 ubiquitinates NLRC5 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Ub ubiquitin Reactome DB_ID: 9929766 Uba52 RPS27A(1-76) P62986 Reactome DB_ID: 9929738 UniProt:P62986 Uba52 UniProt P62986 1 EQUAL 76 EQUAL Reactome Database ID Release 82 9929738 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929738 Reactome R-RNO-939205 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-939205.1 Ubc UBA52(1-76) Q63429 Reactome DB_ID: 9929740 UniProt:Q63429 Ubc UniProt Q63429 1 EQUAL 76 EQUAL Reactome Database ID Release 82 9929740 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929740 Reactome R-RNO-939203 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-939203.1 Ubb UBB(1-76) P0CG51 Reactome DB_ID: 9929742 UniProt:P0CG51 Ubb UniProt P0CG51 1 EQUAL 76 EQUAL Reactome Database ID Release 82 9929742 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929742 Reactome R-RNO-939214 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-939214.1 Rps27a UBC(1-76) P62982 Reactome DB_ID: 9929748 UniProt:P62982 Rps27a UniProt P62982 1 EQUAL 76 EQUAL Reactome Database ID Release 82 9929748 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929748 Reactome R-RNO-939188 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-939188.1 Reactome Database ID Release 82 9929766 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9929766 Reactome R-RNO-113595 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-113595.1 3 ACTIVATION Converted from EntitySet in Reactome TRAF2, TRAF6 Reactome DB_ID: 10020722 Traf2 TRAF2 B5DFH7 Reactome DB_ID: 9936194 UniProt:B5DFH7 Traf2 UniProt B5DFH7 2 EQUAL 501 EQUAL Reactome Database ID Release 82 9936194 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9936194 Reactome R-RNO-66370 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-66370.1 Traf6 TRAF6 B5DF45 Reactome DB_ID: 9942375 UniProt:B5DF45 Traf6 UniProt B5DF45 1 EQUAL 522 EQUAL Reactome Database ID Release 82 9942375 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9942375 Reactome R-RNO-166366 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-166366.1 Reactome Database ID Release 82 10020722 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10020722 Reactome R-RNO-918188 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-918188.1 GENE ONTOLOGY GO:0004842 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 82 10033702 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033702 Reactome Database ID Release 82 10033704 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033704 Reactome R-RNO-9750946 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9750946.1 NOD-like receptor C5 (NLRC5) functions as negative regulator of the NF-kappa B signaling pathway by targeting the I-kappa-B-kinase (IKK) complex (Cui J et al. 2010). The IKK complex consists of two catalytic subunits, IKBKA (KKα or CHUK) and IKBKB (IKKβ), associated with a regulatory subunit IKBKG (NEMO). NLRC5 directly binds to CHUK and IKBKB inhibiting their phosphorylation and interaction with IKBKG (Cui J et al. 2010). The dynamics of NLRC5 interaction with IKBKB/CHUK is regulated by TRAF2 or TRAF6-dependent ubiquitination of NLRC5 (Meng Q et al. 2015). Active TRAF2/6 catalyzed K63-linked polyubiquitination of NLRC5 at K1178 in human and mouse cells in response to LPS stimulation. The ubiquitinated NLRC5 (K63-polyUb-NLRC5) blocked NLRC5 interaction with IKBKB/CHUK thereby resulting in a decreased inhibitory function of NLRC5. The TRAF2/TRAF6-mediated ubiquitination of NLRC5 was reversely regulated by USP14 (Meng Q et al. 2015). LEFT-TO-RIGHT USP14 deubiquitinates NLRC5 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> H2O water Reactome DB_ID: 29356 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 82 29356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356 Reactome R-ALL-29356 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5 COMPOUND C00001 additional information MI MI:0361 3 ACTIVATION GENE ONTOLOGY GO:0061578 Reactome Database ID Release 82 10033699 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033699 Reactome Database ID Release 82 10033701 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033701 Reactome R-RNO-9750942 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9750942.1 NLRC5 functions as negative regulator of the NF-kappa B signaling pathway by targeting the I-kappa-B-kinase (IKK) complex (Cui J et al. 2010). The IKK complex consists of two catalytic subunits, IKBKA (KKα or CHUK) and IKBKB (IKKβ), associated with a regulatory subunit IKBKG (NEMO). NLRC5 directly binds to CHUK and IKBKB inhibiting their phosphorylation and interaction with IKBKG (Cui J et al. 2010). The dynamics of NLRC5 interaction with IKBKB/CHUK is regulated by TRAF2 or TRAF6-dependent K63-linked polyubiquitination of NLRC5 at K1178 (Meng Q et al. 2015). The ubiquitinated NLRC5 (K63-polyUb-NLRC5) showed lower ability to interact with IKBKB/CHUK thereby resulting in a decreased inhibitory function of NLRC5. Ubiquitin-specific protease 14 (USP14) was found to remove the polyUb chains from NLRC5 and thereby enhanced the NLRC5-mediated inhibition of NF-kB signaling (Meng Q et al. 2015). LEFT-TO-RIGHT USP18 binds IKBKG within IKK complex This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Usp18 USP18 Q6AYC7 Reactome DB_ID: 9966389 UniProt:Q6AYC7 Usp18 UniProt Q6AYC7 1 EQUAL 372 EQUAL Reactome Database ID Release 82 9966389 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9966389 Reactome R-RNO-912325 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-912325.1 CHUK:IKBKB:IKBKG:USP18 Reactome DB_ID: 10033912 1 1 Reactome Database ID Release 82 10033912 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033912 Reactome R-RNO-9761338 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9761338.1 Reactome Database ID Release 82 10034018 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10034018 Reactome R-RNO-9761344 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9761344.1 Expression of ubiquitin-specific protease 18 (USP18) is induced by various Toll-like receptor (TLR) ligands in human monocytes and macrophages (Yang Z et al. 2015). A nuclear factor kappa B (NF-kappa-B, NF-κB) luciferase reporter gene assay showed that expression of tagged USP18 negatively regulates TLR-mediated activation of NF-kappa B in human embryonic kidney HEK293T cells. USP18 also inhibited the degradation of endogenous IκBα protein in HEK293T cells (Yang Z et al. 2015). Further, knockdown of USP18 by USP18-specific small interfering RNAs (siRNA) enhanced NF-kappaB activity in LPS- stimulated human monocyte-like THP-1 cells (Yang Z et al. 2015). Co-immunoprecipitation and immunoblot analysis revealed that USP18 targets the regulatory subunit IKBKG (NEMO) of the IKK (CHUK:IKBKB:IKBKG) complex upon co-expression of tagged proteins in HEK293T cells. Mutagenesis analysis using HEK293T cells showed that USP18 directly binds to the UBAN motif of IKBKG inhibiting K63-linked ubiquitination of IKBKG by masking the ubiquitination sites at K325 and K326 (Yang Z et al. 2015). In addition, USP18 targets the TAK1-TAB1 complex and cleaves the K63-linked polyubiquitin chains of TAK1 in a protease-dependent manner (Liu X et al. 2013; Yang Z et al. 2015). These data suggest that USP18 functions as a negative regulator of NF-kappa-B activation.<p>This Reactome events shows USP18 binding to IKBKG within the IKK (CHUK:IKBKB:IKBKG) complex. 23825189 Pubmed 2013 USP18 inhibits NF-κB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex Liu, Xikui Li, Hongxiu Zhong, Bo Blonska, Marzenna Gorjestani, Sara Yan, Ming Tian, Qiang Zhang, Dong-Er Lin, Xin Dong, Chen J. Exp. Med. 210:1575-90 26240016 Pubmed 2015 USP18 negatively regulates NF-κB signaling by targeting TAK1 and NEMO for deubiquitination through distinct mechanisms Yang, Zhifen Xian, Huifang Hu, Jiajia Tian, Shuo Qin, Yunfei Wang, Rong-Fu Cui, Jun Sci Rep 5:12738 LEFT-TO-RIGHT N4BP1 binds IKBKG This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> N4bp1 N4BP1 D3ZT79 Reactome DB_ID: 10033889 UniProt:D3ZT79 N4bp1 UniProt D3ZT79 1 EQUAL 896 EQUAL Reactome Database ID Release 82 10033889 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033889 Reactome R-RNO-9757941 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9757941.1 IKBKG:N4BP1 Reactome DB_ID: 10033898 1 1 Reactome Database ID Release 82 10033898 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033898 Reactome R-RNO-9757950 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9757950.1 Reactome Database ID Release 82 10033900 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033900 Reactome R-RNO-9757954 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9757954.1 NEDD4-binding protein 1 (N4BP1) negatively regulates Toll-like receptor (TLR)-induced activation of NF-kappaB and cytokine production in human and mouse cells (Shi H et al. 2021; Gitlin AD et al. 2020). N4BP1 was found to target IKBKG (NEMO, IKKg), the regulatory subunit of the IkB kinase (IKK) complex, which is essential for NF-kappa-B activation. N4BP1 co-immunoprecipitated with IKBKG (NEMO) upon co-expression of tagged proteins in human embryonic kidney 293T (HEK293T) cells (Shi H et al. 2021). The interaction between endogenous N4BP1 and IKBKG was also detected in mouse peritoneal macrophages (Shi H et al. 2021). Linear and K63-linked polyubiquitin chains promoted the interaction between N4BP1 and IKBKG. Binding of N4BP1 to IKBKG is thought to block homooligomerization of IKBKG thereby leading to destabilization of the IKK complex (Shi H et al. 2021). In addition, N4BP1 deficiency in mice and mouse cells increased the production of select NF-kappa-B-dependent cytokines via TICAM1 (TRIF)-independent TLR2, TLR7 or TLR9 signaling pathways, but not upon engagement of TLR3 or TLR4 which utilize the adaptor protein TICAM1 (Shi H et al. 2021; Gitlin AD et al. 2020). Similar results were observed in human monocytic THP-1 cells (Shi H et al. 2021). Further, TLR3- or TRL4-induced TICAM1-dependent activation of caspase-8 (CASP8) was found to inactivate N4BP1 via the proteolytic cleavage thus promoting NF-kappa-B activation (Gitlin AD et al. 2020; Shi H et al. 2021). Downregulation of N4BP1 was not observed in TICAM-1-deficient mouse macrophages treated with LPS (Shi H et al. 2021). These data suggest that N4BP1 limits TICAM1-independent TLR-induced NF-kappa-B activation by blocking the function of the IKK complex, while TICAM1-dependent TLR signaling leads to CASP8-mediated inactivation of N4BP1(Shi H et al. 2021; Gitlin AD et al. 2020). 32971525 Pubmed 2020 Integration of innate immune signalling by caspase-8 cleavage of N4BP1 Gitlin, Alexander D Heger, Klaus Schubert, Alexander F Reja, Rohit Yan, Donghong Pham, Victoria C Suto, Eric Zhang, Juan Kwon, Youngsu C Freund, Emily C Kang, Jing Pham, Anna Caothien, Roger Bacarro, Natasha Hinkle, Trent Xu, Min McKenzie, Brent S Haley, Benjamin Lee, Wyne P Lill, Jennie R Roose-Girma, Merone Dohse, Monika Webster, Joshua D Newton, Kim Dixit, Vishva M Nature 587:275-280 33654074 Pubmed 2021 N4BP1 negatively regulates NF-κB by binding and inhibiting NEMO oligomerization Shi, Hexin Sun, Lei Wang, Ying Liu, Aijie Zhan, Xiaoming Li, Xiaohong Tang, Miao Anderton, Priscilla Hildebrand, Sara Quan, Jiexia Ludwig, Sara Moresco, Eva Marie Y Beutler, B Nat Commun 12:1379 INHIBITION Reactome Database ID Release 82 10033901 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033901 active caspase-8 Reactome DB_ID: 9938617 Caspase-8 dimer Reactome DB_ID: 9938615 Casp8 CASP8(217-374) Q9JHX4 Reactome DB_ID: 9938611 UniProt:Q9JHX4 Casp8 UniProt Q9JHX4 217 EQUAL 374 EQUAL Reactome Database ID Release 82 9938611 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9938611 Reactome R-RNO-75975 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-75975.1 1 Casp8 CASP8(385-479) Q9JHX4 Reactome DB_ID: 9938613 385 EQUAL 479 EQUAL Reactome Database ID Release 82 9938613 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9938613 Reactome R-RNO-76158 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-76158.1 1 Reactome Database ID Release 82 9938615 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9938615 Reactome R-RNO-139950 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-139950.1 2 Reactome Database ID Release 82 9938617 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9938617 Reactome R-RNO-2562550 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-2562550.1 LEFT-TO-RIGHT 3.4 CASP8 cleaves N4BP1 at D424, D490 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> 2 N4bp1 N4BP1(1-424) D3ZT79 Reactome DB_ID: 10033891 1 EQUAL 424 EQUAL Reactome Database ID Release 82 10033891 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033891 Reactome R-RNO-9757940 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9757940.1 ACTIVATION GENE ONTOLOGY GO:0008234 Reactome Database ID Release 82 10033894 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033894 Reactome Database ID Release 82 10033896 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10033896 Reactome R-RNO-9757951 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9757951.1 GENE ONTOLOGY GO:0043122 NEDD4-binding protein 1 (N4BP1) limits the activation of NF-kappaB downstream of TICAM1 (TRIF)-independent Toll-like receptor 2 (TLR2), TLR7 or TLR9 signaling pathways, but not upon engagement of TLR3 or TLR4 which utilize the adaptor protein TICAM1 (Shi H et al. 2021; Gitlin AD et al. 2020). TLR3- or TRL4-induced TICAM1-dependent activation of caspase-8 (CASP8) was found to inactivate N4BP1 via the proteolytic cleavage thus promoting NF-kappa-B activation (Gitlin AD et al. 2020; Shi H et al. 2021). Functional studies of N4BP1 mutants expressed in human embryonic kidney 293T (HEK293T) cells suggest that human N4BP1 is cleaved after D424 and/or D490 (Shi H et al. 2021). Reactome Database ID Release 82 10037534 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10037534 Reactome R-RNO-9758274 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9758274.1 Nuclear factor kappa B (NF-kappa-B, NF-κB) is activated by a diverse range of stimuli including cytokines, ligands of pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs) in myeloid cells, antigen-activated TCR in T-cells and by DNA damage (reviewed in Yu H et al. 2020; Zhang T et al. 2021). NF-kappa-B regulates the transcription of genes that are involved in immune and inflammatory responses, cell cycle, cell proliferation and apoptosis (Bhatt D & Ghosh S 2014; Liu T et al. 2017; Yu H et al. 2020). In unstimulated cells, NF-κB is sequestered in the cytosol through interactions with a class of inhibitor proteins, called NF-κB inhibitors (IkBs, such as NFKBIA or NFKBIB) (Jacobs MD & Harrison SC 1998). IkBs mask the nuclear localization signal (NLS) of NF-κB preventing its nuclear translocation (Cervantes CF et al. 2011). A key event in NF-κB activation involves phosphorylation of IkBs by the IκB kinase (IKK) complex which consists of CHUK, IKBKB and IKBKG subunits (Israël A 2010). The activated NF-κB signaling is tightly controlled at multiple levels (Dorrington MG & Fraser IDC 2019; Prescott JA et al. 2021). Dysregulated NF-κB activity can cause tissue damage associated with inflammatory diseases and is also linked to tumorigenesis (Aggarwal BB & Sung B 2011; Liu T et al.2017; Barnabei L et al. 2021). The regulation of NF-κB is cell-type-, context- , and stimulus-dependent and is crucial for orchestrating specific cellular responses (Mussbacher M et al. 2019).<p>This Reactome module describes several molecular mechanisms that regulate TLR-mediated NF-κB signaling at the level of the IKK signaling complex. <br><br> 9865693 Pubmed 1998 Structure of an IkappaBalpha/NF-kappaB complex Jacobs, M D Harrison, S C Cell 95:749-58 34977871 Pubmed 2021 NF-κB signaling in inflammation and cancer Zhang, Tao Ma, Chao Zhang, Zhiqiang Zhang, Huiyuan Hu, Hongbo MedComm (2020) 2:618-653 24611065 Pubmed 2014 Regulation of the NF-κB-Mediated Transcription of Inflammatory Genes Bhatt, Dev Ghosh, Sankar Front Immunol 5:71 22586649 Pubmed 2011 NF-κB in cancer: a matter of life and death Aggarwal, Bharat B Sung, Bokyung Cancer Discov 1:469-71 34269817 Pubmed 2021 Inhibitory feedback control of NF-κB signalling in health and disease Prescott, Jack A Mitchell, Jennifer P Cook, Simon J Biochem J 478:2619-2664 32958760 Pubmed 2020 Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study Yu, Hui Lin, Liangbin Zhang, Zhiqiang Zhang, Huiyuan Hu, Hongbo Signal Transduct Target Ther 5:209 31024544 Pubmed 2019 NF-κB Signaling in Macrophages: Dynamics, Crosstalk, and Signal Integration Dorrington, Michael G Fraser, Iain D C Front Immunol 10:705 29158945 Pubmed 2017 NF-κB signaling in inflammation Liu, Ting Zhang, Lingyun Joo, Donghyun Sun, Shao-Cong Signal Transduct Target Ther 2: 34434197 Pubmed 2021 NF-κB: At the Borders of Autoimmunity and Inflammation Barnabei, Laura Laplantine, Emmanuel Mbongo, William Rieux-Laucat, Frederic Weil, Robert Front Immunol 12:716469 30778349 Pubmed 2019 Cell Type-Specific Roles of NF-κB Linking Inflammation and Thrombosis Mussbacher, Marion Salzmann, Manuel Brostjan, Christine Hoesel, Bastian Schoergenhofer, Christian Datler, Hannes Hohensinner, Philipp Basílio, José Petzelbauer, Peter Assinger, Alice Schmid, Johannes A Front Immunol 10:85 21094161 Pubmed 2011 The RelA nuclear localization signal folds upon binding to IκBα Cervantes, Carla F Bergqvist, Simon Kjaergaard, Magnus Kroon, Gerard Sue, Shih-Che Dyson, H Jane Komives, Elizabeth A J. Mol. Biol. 405:754-64 20300203 Pubmed 2010 The IKK complex, a central regulator of NF-kappaB activation Israel, A Cold Spring Harb Perspect Biol 2:a000158