Hsp70 and CHIP Selectively Mediate Ubiquitination and Degradation of Hypoxia-inducible Factor (HIF)-1α but Not HIF-2α

作者: Weibo Luo , Jun Zhong , Ryan Chang , Hongxia Hu , Akhilesh Pandey

DOI: 10.1074/JBC.M109.068577

关键词: Hypoxia-inducible factorsHsp70BiologyRNA interferenceUbiquitinGene expressionBiochemistryImmunoprecipitationCell biologyTranscription factorUbiquitin ligase

摘要: Hypoxia-inducible factors (HIFs) are transcription that mediate adaptive responses to reduced oxygen availability. HIF-α subunits stabilized under conditions of acute hypoxia. However, prolonged hypoxia leads decay HIF-1α but not HIF-2α protein levels by unknown mechanisms. Here, we identify Hsp70 and CHIP (carboxyl terminus Hsc70-interacting protein) as HIF-1α-interacting proteins. Hsp70, through recruiting the ubiquitin ligase CHIP, promotes ubiquitination proteasomal degradation HIF-2α, thereby inhibiting HIF-1-dependent gene expression. Disruption Hsp70-CHIP interaction blocks mediated CHIP. Inhibition or synthesis RNA interference increases attenuates during Thus, Hsp70- CHIP-dependent represents a molecular mechanism which selectively reduces protein.

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