Reactome | 26S proteasome degrades HIFalpha

26S proteasome degrades HIFalpha

Stable Identifier

R-HSA-9755303

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Destruction of ubiquitinated HIF-alpha can occur in both the cytosol and nucleus (Berra et al. 2001). Upon reoxygenation of hypoxic cells HIF-alpha is ubiquitinated in the nucleus and transported to the cytosol in a complex with VHL:ElonginB:ElonginC:CUL2:RBX1 where it is destroyed (Groulx and Lee 2002, Jaakkola et al. 2001, Ivan 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 Pouysségur, J, Roux, D, Richard, DE, Berra, E	EMBO Rep	2001
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
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