Search results for NCOR2

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Reaction (5 results from a total of 11)

Identifier: R-HSA-3777129
Species: Homo sapiens
Compartment: nucleoplasm
HDAC3 mediates the gene silencing activity of Retinoic acid and thyroid hormone receptor (SMRT) complex or the homologous nuclear receptor corepressor (NCoR). These coregulators are involved in a wide range of developmental and homeostatic processes, including metabolism, inflammation, and circadian rhythms (Mottis et al. 2013). HDAC3 interacts with a conserved SANT-like domain known as the deacetylase activating domain (DAD) within NCOR2 (SMRT) or NCOR1 (Li et al. 2000, Wen et al. 2000, Zhang et al. 2002, Yoon et al. 2003, Oberoi et al. 2011). This interaction both recruits and activates HDAC3 (Wen et al. 2000, Guenther et al. 2001, Zhang et al. 2002). Recruitment of HDAC3 to the DAD is essential for repression by the nuclear thyroid hormone receptor and for the maintenance of normal circadian physiology (You et al. 2010, Yin et al. 2007). A second SANT-like domain has been reported to interact directly with histone tails and termed the histone interaction domain (HID) (Hartman et al. 2005, Yu et al. 2003). NCORs are largely unstructured platform proteins that act as a scaffold upon which the enzymatic machinery of the repression complex is built (Watson et al. 2012). They can recruit other deacetylases such as HDAC4 (Fischle et al. 2002), HDAC5, HDAC7 (Kao et al. 2000), Sirt1 (Picard et al. 2004), and via mSin3, HDAC1 (Heinzel et al. 1997, Nagy et al. 1997). The importance of these deacetylase enzymes is not yet established. It has been demonstrated HDAC3 was shown to be responsible for deacetylase activities associated with HDAC4 and HDAC7 (Fischle et al. 2002). Corepressor complexes are heterogeneous, context-specific and transient in nature, but in addition to HDAC3, some additional partners are regularly found in stoichiometric association with NCOR1/NCOR2 and are essential for repressive function. These partners include the G protein pathway suppressor (GPS2) and transducing beta-like 1 (TBL1) and its homologue, TBL-related 1 (TBLR1), which together form the core repression complex (Oberoi et al. 2011). Ins(1,4,5,6)P4 is a further component of the complex (Watson et al. 2012).
Identifier: R-HSA-1912388
Species: Homo sapiens
Compartment: nucleoplasm
In the absence of NICD1, RBPJ (CSL) is bound to a co-repressor complex that includes NCOR proteins, NCOR1 and/or NCOR2 (also known as SMRT) and HDAC histone deacetylases. Both NCOR and HDAC proteins interact with RBPJ (CSL) through a repression domain in RBPJ. When bound to the co-repressor complex, RBPJ (CSL) represses transcription of NOTCH target genes (Kao et al. 1998). The co-repressor complex also contains SNW1 (SKIP), which interacts with RBPJ (CSL) in a repression-domain independent way (Zhou et al. 2000), TBL1X (TBL1) and TBL1XR1 (TBLR1) (Perissi et al. 2004). NICD1 binds to RBPJ (CSL) and SNW1 (SKIP) and displaces NCOR and HDAC proteins (Kao et al. 1998). TBL1X and TBL1XR1 facilitate displacement of NCOR and HDAC and positively regulated NOTCH-mediated transcription probably by recruiting the ubiquitin/19S proteasome complex that degrades transcriptional repressors (Perissi et al. 2004, Perissi et al. 2008). SNW1 facilitates NICD1 interaction with RBPJ and NOTCH-mediated transcription (Zhou et al. 2000). It is possible that the co-repressor complex contains additional proteins not described here. Loss-of-function mutations in RBPJ typically result in phenotypes associated with reduced NOTCH function, suggesting that RBPJ activation complex (i.e. NOTCH coactivator complex) is more important than RBPJ repressor complex in control of normal development and homeostasis (Oka et al. 1995).
Identifier: R-HSA-350058
Species: Homo sapiens
Compartment: nucleoplasm
Mammalian CSL Corepressor Complexes: In the absence of activated Notch signaling, DNA-bound CSL proteins recruit a corepressor complex to maintain target genes in the repressed state until Notch is specifically activated. The mammalian corepressor complexes include NCOR complexes, but may also include additional corepressor proteins, such as SHARP (reviewed in Mumm, 2000 and Kovall, 2007). The exact composition of the CSL NCOR complex is not known, but in other pathways the "core" NCOR corepressor complex includes at least one NCOR protein (NCOR1, NCOR2, CIR), one Histone Deacetylase protein (HDAC1, HDAC3, or certain others), and one TBL1 protein (TBL1X, TBL1XR1) (reviewed in Rosenfeld, 2006). In some contexts, the core NCOR corepressor complex may also recruit additional corepressor proteins or complexes, such as the SIN3 complex, which consists of SIN3 (SIN3A, SIN3B), and SAP30, or other SIN3-associated proteins. An additional CSL - NCOR binding corepressor, SHARP, may also contribute to the CSL corepressor complex in some contexts (Oswald, 2002). The CSL corepressor complex also includes a bifunctional cofactor, SKIP, that is present in both CSL corepressor complexes and CSL coactivator complexes, and may function in the binding of NICD and displacement of the corepressor complex during activated Notch signaling (Zhou, 2000). The formation of the CSL-NCOR corepressor complexes is modelled here as the simultaneous assembly of the various components shown. The order of addition of components is not known, and may vary in different contexts.
Identifier: R-HSA-381309
Species: Homo sapiens
Compartment: nucleoplasm
PPARG can be activated in cell cultures by adding ligands such as polyunsaturated fatty acids and certain prostanoids (prostaglandins). Endogenous fatty acids are relatively poor activators. Which ligands are most responsible for PPARG activation in the body has not yet been established. Generally, oxidized fatty acids such as 9(S')-hydroxyoctadeca-10,12-dienoic acid (9(S')-HODE) and 13(S')-HODE are more effective activators than are endogenous fatty acids. The thiazolidinedione (TZD) class of antidiabetic drugs are agonist ligands for PPARG (Lambe and Tugwood 1996).
FABP4 delivers ligands to PPARG directly. Binding of activator ligands to PPARG causes loss of corepressors such as SMRT/NCoR2, NCoR1, and HDAC3 and gain of interactions with the basal transcription machinery (Yoo et al. 2006). The TRAP220/MED1/DRIP205 subunit of the TRAP/Mediator (DRIP) complex binds directly to the LXXLL motif of PPARG and TRAP/Mediator is necessary for full transcriptional activation of target genes (Ge et al. 2008). PPARG also interacts with the MED14 subunit of the Mediator complex (Grontved et al. 2010).
Other coactivators, including NCOA1/SRC-1, NCOA2/TIF2/GRIP1, CBP, HAT/p300, and PRIP, interact with PPARG in a ligand-dependent way and enhance transcription (Gellman et al. 1999, Wallberg et al. 2003, Yang et al. 2000, Ge et al. 2002, Puigserver et al. 1999, Bugge et al. 2009, Steger et al. 2010).
The target genes of PPARG encode proteins involved in adipocyte differentiation (PGAR/ANGPTL4, PLIN, and aP2/FABP4), carbohydrate metabolism (PEPCK-C), and fatty acid transport (FAT/CD36, LPL).
Identifier: R-HSA-9024334
Species: Homo sapiens
Compartment: nucleoplasm
In the unliganded state, NR1H2,3 (LXR):RXR heterodimers are bound to DNA response elements in association with co-repressor complexes resulting in repression of target genes such as the ATP-binding cassette transporter (ABCA1) gene (Wagner BL et al. 2003; Jakobsson T et al. 2009). Ligand binding to NR1H2,3 induces conformational changes leading to release of co-repressor complexes and recruitment of co-activator complexes and transcription of target genes. A mammalian two-hybrid analysis, using GAL4 fusions of the receptor interacting domains (ID) from the nuclear receptor corepressor (NCOR1) and the silencing mediator of retinoic acid and thyroid hormone receptors (SMRT, also known as NCOR2) transiently co-expressed with VP-16 fusions of NR1H3 or NR1H2 ligand binding domains in the monkey kidney fibroblasts CV-1 cells showed that in the absence of ligand, both NR1H2 and NR1H3 interacted with the corepressor IDs of NCOR and SMRT (Wagner BL et al. 2003). Biochemical work has identified a core complex consisting of NCOR, histone deacetylase 3 (HDAC3), transducin β-like proteins (TBL1, TBLR1), and G protein pathway suppressor 2 (GPS2) (Zhang J et al. 2002). Chromatin immunoprecipitation (ChIP) assays in HepG2 cells revealed that, in the absence of GW3965, a synthetic NR1H2,3 agonist, NCOR and HDAC3 were associated with the ABCA1 promoter, while agonist treatment caused their dissociation and induced recruitment of histone acetyltransferase (HAT) CBP and RNA polymerase II (Jakobsson T et al. 2009). TBLR1 was also present at the promoter and unaffected by the ligand status. GPS2 was found to occupy the ABCA1 promoter in the absence of ligand but was released upon GW3965 treatment, while NR1H2,3 (LXR) recruitment was observed already in the absence of ligand and further enhanced upon ligand activation (Jakobsson T et al. 2009). The inclusion of anti-RXR antibody in the re-ChIP assays demonstrates that GPS2 associates with the LXR:RXR heterodimer. Importantly, similar recruitment patterns were obtained in human THP-1 macrophages. Thus, at the ABCA1 promoter, NR1H2,3 ligand triggers exchange of a GPS corepressor complex (containing NCoR, HDAC3, TBLR1) for the coactivator complex devoid of GPS2 (Jakobsson T et al. 2009).
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