AcM-UBE2F transfers NEDD8 to CRL5 E3 ubiquitin ligase complex

Stable Identifier
Reaction [transition]
Homo sapiens
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UBE2F transfers NEDD8 to lysine 724 of CUL5 in the E3 ligase complex (Duda et al, 2008). Neddylation increases the ubiquitination activity of the E3 complex towards its target, and prevents binding of the CUL5 complex with the CAND1 inhibitor (Hori et al, 1999; Duda et al, 2008; Kelsall et al, 2013). Targets of CUL5 RING complexes include a variety of cellular proteins including receptor and non-receptor tyrosine kinases, signaling molecules transcriptional regulators (reviewed in Okamura et al, 2016). CRL5 complexes are also hijacked by viruses such as HIV, HPV and adenovirus among others. Interaction with viral proteins redirects the ubiquitin ligase complex to target host proteins to promote conditions that favor viral propagation (Harada et al, 2002; Mehle et al, 2004; reviewed in Mahon et al, 2014).

Literature References
PubMed ID Title Journal Year
15574592 Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation

Santa-Marta, M, Goncalves, J, Gabuzda, D, McPike, M, Mehle, A

Genes Dev 2004
25314029 Cullin E3 ligases and their rewiring by viral factors

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

Biomolecules 2014
12186903 Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery

Berk, AJ, Pallas, DC, Harada, JN, Shevchenko, A, Shevchenko, A

J. Virol. 2002
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
24076655 TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes

Hofmann, K, Alpi, AF, Duda, DM, Schulman, BA, Knebel, A, Wood, N, Kelsall, IR, Wightman, M, Olszewski, JL, Langevin, F

EMBO J. 2013
27030794 The role of cullin 5-containing ubiquitin ligases

Okumura, F, Kamura, T, Joo-Okumura, A, Nakatsukasa, K

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
Catalyst Activity

NEDD8 transferase activity of NEDD8-AcM-UBE2F:CRL5 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1Ds [cytosol]

Orthologous Events
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