AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
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
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
26344709 Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B

Zhou, P, Hannah, J

Gene 2015
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
Catalyst Activity

NEDD8 transferase activity of NEDD8-AcM-UBE2M:CRL4 E3 ubiquitin ligase:COMMDs:CCDC22:DCUND1,2,4,5 [nucleoplasm]

Orthologous Events
Cite Us!