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

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

Stable Identifier

R-HSA-1234169

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The VHL component of the VHL:ElonginB:ElonginC:CUL2:RBX1 binds HIF-alpha 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, Bonicalzi et al. 2001). The VHL:HIF-alpha complex is predominantly nuclear (Lewis and Roberts 2003) however binding and degradation of HIF-alpha can also occur in the cytosol (Berra et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
10823831	Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein Masson, N, Chang, GW, Mole, DR, Jaakkola, P, Maxwell, PH, Cockman, ME, Maher, ER, Pugh, CW, Clifford, SC, Ratcliffe, PJ	J Biol Chem	2000
11024059	Role of exon 2-encoded beta -domain of the von Hippel-Lindau tumor suppressor protein Lee, S, de Paulsen, N, Groulx, I, Bonicalzi, ME	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 Pouysségur, J, Roux, D, Richard, DE, Berra, E	EMBO Rep	2001
10944113	Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein Poellinger, L, Pereira, T, Tanimoto, K, Makino, Y	EMBO J	2000
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
11292862	HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing Lane, WS, Asara, JM, Kim, W, Salic, A, Valiando, J, Ivan, M, Kaelin WG, Jr, Ohh, M, Kondo, K, Yang, H	Science	2001
11292861	Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation Gielbert, J, Gaskell, SJ, Maxwell, PH, Mukherji, M, Pugh, CW, Mole, DR, Kriegsheim, Av, Jaakkola, P, Tian, YM, Wilson, MI, Hebestreit, HF, Schofield, CJ, Ratcliffe, PJ	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
12821933	Role of nuclear and cytoplasmic localization in the tumour-suppressor activity of the von Hippel-Lindau protein Roberts, BJ, Lewis, MD	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
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 Chen, DY, Worrell, RA, Burgess, WH, Lee, S, Linehan, WM, Klausner, RD, Pause, A	Proc Natl Acad Sci U S A	1997
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