Reactome | AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex

AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex

Stable Identifier

R-HSA-8952638

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex

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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 Mahon, C, Krogan, NJ, Craik, CS, Pick, E	Biomolecules	2014
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
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