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).
Santa-Marta, M, Goncalves, J, Gabuzda, D, McPike, M, Mehle, A
Pick, E, Mahon, C, Krogan, NJ, Craik, CS
Berk, AJ, Pallas, DC, Harada, JN, Shevchenko, A, Shevchenko, A
Kato, S, Shimbara, N, Miyamoto, C, Osaka, F, Okabayashi, K, Chiba, T, Tanaka, K, Hori, T
Hofmann, K, Alpi, AF, Duda, DM, Schulman, BA, Knebel, A, Wood, N, Kelsall, IR, Wightman, M, Olszewski, JL, Langevin, F
Okumura, F, Kamura, T, Joo-Okumura, A, Nakatsukasa, K
Borg, LA, Hunt, HW, Duda, DM, Schulman, BA, Hammel, M, Scott, DC
NEDD8 transferase activity of NEDD8-AcM-UBE2F:CRL5 E3 ubiquitin ligase:COMMDs:CCDC22:DCUN1Ds [cytosol]
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