AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex

Stable Identifier
R-HSA-8952638
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

UBE2M transfers NEDD8 to lysine 705 of CUL4A and lysine 859 of CUL4B (Hori et al, 1999; Duda et al, 2008). Neddylation increases the ubiquitination activity of the E3 complex towards its targets, and prevents binding of the CUL4 complex with the CAND1 inhibitor (Hori et al, 1999; Duda et al, 2008). 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 (reveiwed 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
10597293 Covalent modification of all members of human cullin family proteins by NEDD8

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

Oncogene 1999
25314029 Cullin E3 ligases and their rewiring by viral factors

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

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

Sang, Y, Yan, F, Ren, X

Oncotarget 2015
26344709 Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B

Hannah, J, Zhou, P

Gene 2015
18805092 Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation

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

Cell 2008
Participants
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
NEDD8 transferase activity of NEDD8-AcM-UBE2M:CRL4 E3 ubiquitin ligase:COMMDs:CCDC22:DCUND1,2,4,5 [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed