Reactome | NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex

NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex

Stable Identifier

R-HSA-8952620

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex

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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 CUL1 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 CRL1 complex is directed by the nature of the F box substrate recognition protein, of which there are more than 60 in humans. Identified targets of CRL1-containing complexes include signaling molecules, transcriptional regulators and regulators of cell cycle progression, among others (reviewed in Gutierrez and Ronai, 2006; Lipkowitz and Weissman, 2011). CRL1 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 (reveiwed 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
16647857	Ubiquitin and SUMO systems in the regulation of mitotic checkpoints Gutierrez, GJ, Ronai, Z	Trends Biochem. Sci.	2006
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
21863050	RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis Lipkowitz, S, Weissman, AM	Nat. Rev. Cancer	2011
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
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
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
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