NEDD8:AcM-UBE2F binds CRL5 E3 ubiquitin ligase complex

Stable Identifier
Reaction [binding]
Homo sapiens
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UBE2F is specific for the CUL5:RBX2-containing E3 ligase complex (Huang et al, 2009; Monda et al, 2013). Interaction between UBE2F and the CUL5 E3 complex is facilitated by a DCUN1D (also known as DCNL) scaffold protein, of which there are 5 in human cells (Kim et al, 2008; Kurz et al, 2008; Meyer-Schaller et al, 2009; Monda et al, 2013; Keuss et al, 2016). DCUN1D proteins interact with higher affinity to the N-terminally acetylated forms of UBE2F and UBE2M (Scott et al, 2011; Monda et al, 2013). Although each of the 5 DCUN1D proteins appears to interact with most cullin subtypes, specificity may arise through differences in expression and localization, and DCUN1D3 may play a specialized role in sequestering CRL E3 ligase complexes at the cell membrane (Monda et al, 2013; Keuss et al, 2016; Meyer-Schaller et al, 2009; Huang et al, 2014; reviewed in Enchev et al, 2103). Although in this pathway, COMMD proteins and DCUN1D are shown acting sequentially in the activation of the CRL E3 ligase complex, the relationship between these protein families is not totally clear, as DCUN1D proteins have been identified in complexes that also contain the inhibitor CAND1 (Kim et al, 2008; Huang et al, 2014).
CUL5 RING complexes target a variety of cellular proteins for ubiquitination and degradation, including receptor and non-receptor tyrosine kinases, signaling molecules transcriptional regulators (reviewed in Okumura et al, 2016). CRL5 complexes are also hijacked by viruses such as HIV and HPV, among others. Interaction with viral proteins redirects the ubiquitin ligase complex, targeting host proteins such as immune factors and in this way promoting viral propagation (reveiwed in Mahon et al, 2014).

Literature References
PubMed ID Title Journal Year
25314029 Cullin E3 ligases and their rewiring by viral factors

Mahon, C, Krogan, NJ, Craik, CS, Pick, E

Biomolecules 2014
23201271 Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes

Monda, JK, Scott, DC, Miller, DJ, Lydeard, J, King, D, Harper, JW, Bennett, EJ, Schulman, BA

Structure 2013
18206966 Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation

Kurz, T, Chou, YC, Willems, AR, Meyer-Schaller, N, Hecht, ML, Tyers, M, Peter, M, Sicheri, F

Mol. Cell 2008
19617556 The human Dcn1-like protein DCNL3 promotes Cul3 neddylation at membranes

Meyer-Schaller, N, Chou, YC, Sumara, I, Martin, DD, Kurz, T, Katheder, N, Hofmann, K, Berthiaume, LG, Sicheri, F, Peter, M

Proc. Natl. Acad. Sci. U.S.A. 2009
18826954 SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation

Kim, AY, Bommeljé, CC, Lee, BE, Yonekawa, Y, Choi, L, Morris, LG, Huang, G, Kaufman, A, Ryan, RJ, Hao, B, Ramanathan, Y, Singh, B

J. Biol. Chem. 2008
25531226 Protein neddylation: beyond cullin-RING ligases

Enchev, RI, Schulman, BA, Peter, M

Nat. Rev. Mol. Cell Biol. 2015
25349211 SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1)

Huang, G, Stock, C, Bommeljé, CC, Weeda, VB, Shah, K, Bains, S, Buss, E, Shaha, M, Rechler, W, Ramanathan, SY, Singh, B

J. Biol. Chem. 2014
27030794 The role of cullin 5-containing ubiquitin ligases

Okumura, F, Joo-Okumura, A, Nakatsukasa, K, Kamura, T

Cell Div 2016
21940857 N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex

Scott, DC, Monda, JK, Bennett, EJ, Harper, JW, Schulman, BA

Science 2011
26906416 Characterization of the mammalian family of DCN-type NEDD8 E3 ligases

Keuss, MJ, Thomas, Y, Mcarthur, R, Wood, NT, Knebel, A, Kurz, T

J. Cell. Sci. 2016
19250909 E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification

Huang, DT, Ayrault, O, Hunt, HW, Taherbhoy, AM, Duda, DM, Scott, DC, Borg, LA, Neale, G, Murray, PJ, Roussel, MF, Schulman, BA

Mol. Cell 2009
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