AcM-UBE2M transfers NEDD8 to CRL2 E3 ubiquitin ligase complex

Stable Identifier
R-HSA-8952626
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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General
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UBE2M transfers NEDD8 to lysine 689 of CUL2 in the E3 ligase complex (Hori et al, 1999; Duda et al, 2008). Neddylation increases the ubiquitin ligase activity of the E3 complex towards its targets, and prevents binding of the CUL2 complex with the CAND1 inhibitor (Hori et al, 1999; Duda et al, 2008).
Target specificity of the CRL2 complex is directed by the nature of the F box substrate recognition protein. The best characterized CRL2 F-box protein is the von Hippel- Lindau (VHL) tumor suppressor, which targets the alpha subunit of hypoxia inducible factor (HIFalpha), among other substrates (reviewed in Cai and Yang, 2016). Another example if CRL2/HRD1 that has been reported to target NFE2L2 for degradation in liver (Wu et al, 2014). CRL2 complexes are hijacked by a number of viruses, including adenovirus, Epstein-Barr virus and HPV, among others. This redirects the ubiquitin ligase complex to target host proteins and in this way promotes viral propagation (reviewed in Mahon et al, 2014).
Literature References
PubMed ID Title Journal Year
25314029 Cullin E3 ligases and their rewiring by viral factors

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

Biomolecules 2014
10597293 Covalent modification of all members of human cullin family proteins by NEDD8

Kato, S, Shimbara, N, Miyamoto, C, Osaka, F, Okabayashi, K, Chiba, T, Tanaka, K, Hori, T

Oncogene 1999
24636985 Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis

Gao, B, Tan, C, Zhang, DD, Chapman, E, Yagishita, N, Zhao, F, Wu, T, Wong, PK, Nakajima, T, Fang, D

Genes Dev 2014
27222660 The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions

Cai, W, Yang, H

Cell Div 2016
18805092 Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation

Borg, LA, Hunt, HW, Duda, DM, Schulman, BA, Hammel, M, Scott, DC

Cell 2008
Participants
Participates
Catalyst Activity

NEDD8 transferase activity of NEDD8-AcM-UBE2M:CRL2 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1D1,2,4,5 [cytosol]

Orthologous Events
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