VHL:EloB,C:NEDD8-CUL2:RBX1 complex binds hydroxyprolyl-HIF-alpha

Stable Identifier
R-HSA-8956103
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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
10878807 Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein

Ohh, M, Park, CW, Ivan, M, Hoffman, MA, Kim, TY, Huang, LE, Pavletich, N, Chau, V, Kaelin, WG

Nat Cell Biol 2000
10823831 Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein

Cockman, ME, Masson, N, Mole, DR, Jaakkola, P, Chang, GW, Clifford, SC, Maher, ER, Pugh, CW, Ratcliffe, PJ, Maxwell, PH

J Biol Chem 2000
11292861 Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation

Jaakkola, P, Mole, DR, Tian, YM, Wilson, MI, Gielbert, J, Gaskell, SJ, Kriegsheim, Av, Hebestreit, HF, Mukherji, M, Schofield, CJ, Maxwell, PH, Pugh, CW, Ratcliffe, PJ

Science 2001
12821933 Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein

Lewis, MD, Roberts, BJ

Oncogene 2003
11358837 Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein

Yu, F, White, SB, Zhao, Q

Cancer Res 2001
12101228 Oxygen-dependent ubiquitination and degradation of hypoxia-inducible factor requires nuclear-cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein

Groulx, I, Lee, S

Mol Cell Biol 2002
11024059 Role of exon 2-encoded beta -domain of the von Hippel-Lindau tumor suppressor protein

Bonicalzi, ME, Groulx, I, de Paulsen, N, Lee, S

J Biol Chem 2001
11454738 Hypoxia-inducible factor-1 alpha (HIF-1 alpha) escapes O(2)-driven proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm

Berra, E, Roux, D, Richard, DE, Pouysségur, J

EMBO Rep 2001
10944113 Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein

Tanimoto, K, Makino, Y, Pereira, T, Poellinger, L

EMBO J 2000
11292862 HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing

Ivan, M, Kondo, K, Yang, H, Kim, W, Valiando, J, Ohh, M, Salic, A, Asara, JM, Lane, WS, Kaelin WG, Jr

Science 2001
11504942 HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation

Yu, F, White, SB, Zhao, Q

Proc Natl Acad Sci U S A 2001
27222660 The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions

Cai, W, Yang, H

Cell Div 2016
9122164 The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins

Pause, A, Lee, S, Worrell, RA, Chen, DY, Burgess, WH, Linehan, WM, Klausner, RD

Proc Natl Acad Sci U S A 1997
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