Endocytosis is differentially regulated by hypoxia-inducible factor-1α (HIF-1α) and phospholipase D (PLD). However, the relationship between HIF-1α and PLD in endocytosis is unknown. HIF-1α is degraded through the prolyl hydroxylase (PHD)/von Hippel–Lindau (VHL) ubiquitination pathway in an oxygen-dependent manner. Here, we show that PLD1 recovers the decrease in epidermal growth factor receptor (EGFR) endocytosis induced by HIF-1α independent of lipase activity via the Rab5-mediated endosome fusion pathway. EGF-induced interaction of PLD1 with HIF-1α, PHD and VHL may contribute to EGFR endocytosis. The pleckstrin homology domain (PH) of PLD1 itself promotes degradation of HIF-1α, then accelerates EGFR endocytosis via upregulation of rabaptin-5 and suppresses tumor progression. These findings reveal a novel role of the PLD1-PH domain as a positive regulator of endocytosis and provide a link between PLD1 and HIF-1α in the EGFR endocytosis pathway.
|Journal||Experimental and Molecular Medicine|
|Publication status||Published - 2015 Dec|
Bibliographical noteFunding Information:
This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2015R1A2A1A05001884) and a Translational Research Center for Protein Function Control Grant (NSF 2009-0092960) and a National R&D Program for Cancer Control grant from the Ministry for Health, Welfare, and Family Affairs (Republic of Korea; 0920050).
© 2015 KSBMB.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry