NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex

Stable Identifier
Reaction [binding]
Homo sapiens
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UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 and 4 (Huang et al, 2009; Monda et al, 2013). Interaction between UBE2M and the CUL4A and 4B 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).
CRL4 complexes ubiquitinate target proteins involved in processes such as cell cycle progression, DNA repair and replication, cell growth and metabolism (reviewed in Hannah and Zhou, 2015; Sang et al, 2015). CRL4 complexes are also hijacked by a number of viruses, redirecting the ubiquitin ligase complex to target host proteins and in this way promoting viral propagation (reviewed in Mahon et al, 2014). Note that because many of the key CRL4 ubiquitin targets are nuclear, these complexes are depicted in the nucleus. Cytoplasmic targets have also been identified, however (reviewed in Hannah and Zhou, 2015).

Literature References
PubMed ID Title Journal Year
23201271 Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes

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

Structure 2013
25314029 Cullin E3 ligases and their rewiring by viral factors

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

Biomolecules 2014
26460955 The role and mechanism of CRL4 E3 ubiquitin ligase in cancer and its potential therapy implications

Ren, X, Sang, Y, Yan, F

Oncotarget 2015
18206966 Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation

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

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

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

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

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

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

Schulman, BA, Enchev, RI, Peter, M

Nat. Rev. Mol. Cell Biol. 2015
26344709 Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B

Zhou, P, Hannah, J

Gene 2015
25349211 SCCRO3 (DCUN1D3) antagonizes the neddylation and oncogenic activity of SCCRO (DCUN1D1)

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

J. Biol. Chem. 2014
26906416 Characterization of the mammalian family of DCN-type NEDD8 E3 ligases

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

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

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

Mol. Cell 2009
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