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

Stable Identifier
R-HSA-1234183
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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VHL within the VHL:ElonginB:ElonginC:CUL2:RBX1 Complex binds HIF-alpha subunits that have hydroxylated proline residues (Cockman et al. 2000, Ohh et al. 2000, Tanimoto et al. 2000, Jaakkola et al. 2001, Ivan et al. 2001, Yu et al. 2001). VHL constitutively shuttles between the cytosol and nucleoplasm (Lewis and Roberts 2003) and though the VHL:HIF-alpha complex is predominantly nuclear, binding and degradation can occur in both the cytosol and the nucleus (Berra et al. 2001).

Literature References
PubMed ID Title Journal Year
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
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
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
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
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
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
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
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
22286099 The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity

Foxler, DE, Bridge, KS, James, V, Webb, TM, Mee, M, Wong, SC, Feng, Y, Constantin-Teodosiu, D, Petursdottir, TE, Bjornsson, J, Ingvarsson, S, Ratcliffe, PJ, Longmore, GD, Sharp, TV

Nat. Cell Biol. 2012
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