Phospholipase D2 promotes degradation of hypoxia-inducible factor-1α independent of lipase activity

Mi Hee Park, Sun Sik Bae, Kang Yell Choi, Do Sik Min

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hypoxia-inducible factor-1α (HIF-1α) is a key transcriptional mediator that coordinates the expression of various genes involved in tumorigenesis in response to changes in oxygen tension. The stability of HIF-1α protein is determined by oxygen-dependent prolyl hydroxylation, which is required for binding of the von Hippel-Lindau protein (VHL), the recognition component of an E3 ubiquitin ligase that targets HIF-1α for ubiquitination and degradation. Here, we demonstrate that PLD2 protein itself interacts with HIF-1α, prolyl hydroxylase (PHD) and VHL to promote degradation of HIF-1α via the proteasomal pathway independent of lipase activity. PLD2 increases PHD2-mediated hydroxylation of HIF-1α by increasing the interaction of HIF-1α with PHD2. Moreover, PLD2 promotes VHL-dependent HIF-1α degradation by accelerating the association between VHL and HIF-1α. The interaction of the pleckstrin homology domain of PLD2 with HIF-1α also promoted degradaion of HIF-1α and decreased expression of its target genes. These results indicate that PLD2 negatively regulates the stability of HIF-1α through the dynamic assembly of HIF-1α, PHD2 and VHL.

Original languageEnglish
Article numbere196
JournalExperimental and Molecular Medicine
Volume47
Issue number11
DOIs
Publication statusPublished - 2015 Jan 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Phospholipase D2 promotes degradation of hypoxia-inducible factor-1α independent of lipase activity'. Together they form a unique fingerprint.

  • Cite this