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

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

Stable Identifier

R-HSA-1234183

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

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

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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