Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UNIPROT:P50502 (
Hip
)
7,003
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hypoxia-inducible factors (HIFs) are transcription factors that mediate adaptive responses to reduced oxygen availability. HIF-alpha subunits are stabilized under conditions of acute hypoxia. However, prolonged hypoxia leads to decay of
HIF-1alpha
but not HIF-2alpha protein levels by unknown mechanisms. Here, we identify Hsp70 and CHIP (carboxyl terminus of
Hsc70-interacting protein
) as
HIF-1alpha
-interacting proteins. Hsp70, through recruiting the ubiquitin ligase CHIP, promotes the ubiquitination and proteasomal degradation of
HIF-1alpha
but not HIF-2alpha, thereby inhibiting HIF-1-dependent gene expression. Disruption of Hsp70-CHIP interaction blocks
HIF-1alpha
degradation mediated by Hsp70 and CHIP. Inhibition of Hsp70 or CHIP synthesis by RNA interference increases protein levels of
HIF-1alpha
but not HIF-2alpha and attenuates the decay of
HIF-1alpha
levels during prolonged hypoxia. Thus, Hsp70- and CHIP-dependent ubiquitination represents a molecular mechanism by which prolonged hypoxia selectively reduces the levels of
HIF-1alpha
but not HIF-2alpha protein.
...
PMID:Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor (HIF)-1alpha but Not HIF-2alpha. 1994 Jan 51
