Proteasome proteolyzes ub-HIF-alpha

Stable Identifier
R-HSA-1234159
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
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
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
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
12101228 Oxygen-dependent ubiquitination and degradation of hypoxia-inducible factor requires nuclear-cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein

Groulx, I, Lee, S

Mol Cell Biol 2002
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
endopeptidase activity of 26S proteasome [cytosol]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed