VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds UBXN7

Stable Identifier
R-HSA-8956099
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The best characterized CRL2 substrate binding F-box protein is the von Hippel- Lindau (VHL) tumor suppressor, which targets the alpha subunit of hypoxia inducible factor (HIFalpha) for ubiquitination and degradation through VCP/p97 and the 26 S proteasome (Sufan and Ohh, 2006; Heir et al, 2013; reviewed in Cai and Yang, 2016). UBXN7 is an adapter that binds to neddylated CUL2 and interferes with the ability of the CUL2:EloB:EloC:VHL E3 ubiquitin ligase complex to ubiquitinate HIF alpha, in this way causing accumulation of HIF alpha (Bandau et al, 2012; Den Besten et al, 2012)

Literature References
PubMed ID Title Journal Year
17132228 Role of the NEDD8 modification of Cul2 in the sequential activation of ECV complex

Sufan, RI, Ohh, M

Neoplasia 2006
23401859 DCNL1 functions as a substrate sensor and activator of cullin 2-RING ligase

Heir, P, Sufan, RI, Greer, SN, Poon, BP, Lee, JE, Ohh, M

Mol. Cell. Biol. 2013
22466964 NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway

den Besten, W, Verma, R, Kleiger, G, Oania, RS, Deshaies, RJ

Nat. Struct. Mol. Biol. 2012
27222660 The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions

Cai, W, Yang, H

Cell Div 2016
22537386 UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1? accumulation

Bandau, S, Knebel, A, Gage, ZO, Wood, NT, Alexandru, G

BMC Biol. 2012
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