Phospholipase D1 protein coordinates dynamic assembly of HIF-1α-PHD-VHL to regulate HIF-1α stability.

ABSTRACT: Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of cellular response to hypoxia. In normoxia, HIF-1α is degraded through the prolyl hydroxylase (PHD) and von Hippel-Lindau (VHL) ubiquitination pathway. However, it is unknown whether PHD and VHL exert their enzymatic activities on HIF-1α separately or as a multiprotein complex. Here, we show that phospholipase D1 (PLD1) protein itself acts as a molecular platform, interacting directly with HIF-1α, PHD, and VHL, thereby dynamically assembling a multiprotein complex that mediates efficient degradation of HIF-1α in an O2-dependent manner. PLD1 depletion prevents degradation of HIF-1α; however, overall, PLD1 activity is predominantly involved in the upregulation of HIF-1α through increased translation, despite negativ

SUBMITTER: Park MH 

PROVIDER: S-EPMC4323006 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature