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PIAS3 enhances the transcriptional activity of HIF-1α by increasing its protein stability.

Abstract
The transcription factor hypoxia-inducible factor-1 (HIF-1) functions as a master regulator of hypoxic response by inducing the transcription of various genes responsible for cellular adaptation to hypoxia. In this study, we investigated the effects of protein inhibitor of activated STAT3 (PIAS3), a small ubiquitin-related modifier (SUMO) E3 ligase, on HIF-1-mediated transcriptional activation. We found that PIAS3 physically associated with HIF-1α. Moreover, PIAS3 overexpression enhanced the transcriptional activity of HIF-1α independently of its SUMO E3 ligase activity. Conversely, quantitative RT-PCR analysis showed that RNAi-mediated PIAS3 knockdown reduced the expression of HIF-1 target genes under hypoxia. In addition, PIAS3 knockdown induced the destabilization of HIF-1α protein, and the destabilization was reversed by the proteasome inhibitor MG132. Taken together, these results suggest that PIAS3 functions as a positive regulator of HIF-1α-mediated transcription by increasing its protein stability.
AuthorsKoji Nakagawa, Toshihisa Kohara, Yasuko Uehata, Yui Miyakawa, Maremi Sato-Ueshima, Naoto Okubo, Masahiro Asaka, Hiroshi Takeda, Masanobu Kobayashi
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 469 Issue 3 Pg. 470-6 (Jan 15 2016) ISSN: 1090-2104 [Electronic] United States
PMID26697750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Molecular Chaperones
  • PIAS3 protein, human
  • Protein Inhibitors of Activated STAT
Topics
  • HEK293 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Molecular Chaperones (metabolism)
  • Protein Inhibitors of Activated STAT (metabolism)
  • Protein Stability
  • Signal Transduction (physiology)
  • Transcriptional Activation (physiology)

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