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• W2128601907 abstract "// Mi Hee Park 1 , Kang-Yell Choi 2,3 , Yunjin Jung 4 and Do Sik Min 1,3 1 Department of Molecular Biology, Pusan National University, Busan, Republic of Korea 2 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea 3 Translational Research Center for Protein Function Control, Yonsei University, Seoul, Republic of Korea 4 College of Pharmacy, Pusan National University, Busan, Republic of Korea Correspondence: Do Sik Min, email: // Keywords : Phospholipase D1, Hypoxia-inducible factor-1α, Prolyl hydroxylase, Von Hippel-Lindau, Pleckstrin homology domain Received : July 16, 2014 Accepted : October 21, 2014 Published : October 21, 2014 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 O 2 -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 negative regulation of HIF-1α stability by PLD1 protein itself, suggesting dual roles of PLD1 in the regulation of HIF-1α. Disruption of the interactions of PLD1 with the proteins might be involved in hypoxic stabilization of HIF-1α. Interestingly, the pleckstrin homology domain interacting with these proteins promoted degradation of HIF-1α independent of oxygen concentration and suppressed tumor progression. These observations define a novel function of PLD1 as a previously unrecognized HIF-1α regulator." @default.
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• W2128601907 date "2014-10-21" @default.
• W2128601907 modified "2023-09-25" @default.
• W2128601907 title "Phospholipase D1 protein coordinates dynamic assembly of HIF-1α-PHD-VHL to regulate HIF-1α stability" @default.
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• W2128601907 doi "https://doi.org/10.18632/oncotarget.2613" @default.
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