Reactome | VHL:EloB,C:NEDD8-CUL2:RBX1 complex ubiquitinylates HIF-alpha

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

Stable Identifier

R-HSA-8956106

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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

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VHL is the substrate binding protein of a CUL2-based E3 ubiquitin ligase complex that conjugates ubiquitin to hydroxylated HIF-alpha (Iwai et al. 1999, Kamura et al. 2000, Ohh et al. 2000, Groulx and Lee 2002, Maynard et al. 2003). VHL is predominantly cytosolic and shuttles between the cytosol and the nucleus (Lee et al. 1999, Groulx and Lee 2002). Ubiquitination and degradation of HIF-alpha can occur in both the cytosol and the nucleus (Berra et al. 2001). Upon return to normoxia from hypoxia most ubiquitinated HIF-alpha is nuclear (Groulx and Lee 2002).

Literature References

PubMed ID	Title	Journal	Year
12538644	Multiple splice variants of the human HIF-3 alpha locus are targets of the von Hippel-Lindau E3 ubiquitin ligase complex Lee, EH, Chung, J, Maynard, MA, Qi, H, Ohh, M, Conaway, JW, Kondo, Y, Hara, S, Conaway, RC	J Biol Chem	2003
11454738	Hypoxia-inducible factor-1 alpha (HIF-1 alpha) escapes O(2)-driven proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm Pouysségur, J, Roux, D, Richard, DE, Berra, E	EMBO Rep	2001
10973499	Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex Kamura, T, Sato, S, Czyzyk-Krzeska, M, Conaway, JW, Iwai, K, Conaway, RC	Proc Natl Acad Sci U S A	2000
9891082	Transcription-dependent nuclear-cytoplasmic trafficking is required for the function of the von Hippel-Lindau tumor suppressor protein Stearman, R, Pavlakis, GN, Stauber, R, Neumann, M, Klausner, RD, Lee, S, Pause, A	Mol Cell Biol	1999
10878807	Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein Pavletich, N, Kim, TY, Park, CW, Ivan, M, Kaelin, WG, Ohh, M, Huang, LE, Hoffman, MA, Chau, V	Nat Cell Biol	2000
10535940	Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex Kamura, T, Yamanaka, K, Minato, N, Conaway, JW, Klausner, RD, Iwai, K, Conaway, RC, Pause, A	Proc Natl Acad Sci U S A	1999
12101228	Oxygen-dependent ubiquitination and degradation of hypoxia-inducible factor requires nuclear-cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein Lee, S, Groulx, I	Mol Cell Biol	2002