NEDD8:AcM-UBE2M binds CRL3 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 CUL3 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).
Target specificity of the CRL3 complex is directed by the nature of the BTB substrate recognition protein. For instance, BTB protein KEAP1 is the main controller of NFE2L2 stability (Cuadrado et al, 2019). CRL3 complexes target proteins involved in processes such as development and stress response (reviewed in Genschik et al, 2013). CRL3 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).

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
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
23912815 The emerging family of CULLIN3-RING ubiquitin ligases (CRL3s): cellular functions and disease implications

Lechner, E, Sumara, I, Genschik, P

EMBO J. 2013
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
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
21940857 N-terminal acetylation acts as an avidity enhancer within an interconnected multiprotein complex

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

Science 2011
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
30610225 Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases

Wells, G, Cousin, SP, Franklin, S, Cuadrado, A, Rojo, AI, Hayes, JD, Rumsey, WL, Levonen, AL, Dinkova-Kostova, AT, Kensler, TW, Attucks, OC

Nat Rev Drug Discov 2019
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