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

被引：14

作者：

Nakagawa, Koji ^{[1
]}

Kohara, Toshihisa ^{[2
]}

Uehata, Yasuko ^{[2
]}

Miyakawa, Yui ^{[1
]}

Sato-Ueshima, Maremi ^{[1
]}

Okubo, Naoto ^{[1
]}

Asaka, Masahiro ^{[2
,3
]}

Takeda, Hiroshi ^{[1
,2
]}

Kobayashi, Masanobu ^{[3
,4
]}

机构：

[1] Hokkaido Univ, Fac Pharmaceut Sci, Div Pharmasci, Dept Pathophysiol & Therapeut,Kita Ku, N12 W6, Sapporo, Hokkaido 0600812, Japan

[2] Hokkaido Univ, Dept Gastroenterol & Hematol, Grad Sch Med, N15 W7 Kita Ku, Sapporo, Hokkaido 0608638, Japan

[3] Hokkaido Univ, Dept Canc Prevent Med, Grad Sch Med, N15 W7 Kita Ku, Sapporo, Hokkaido 0608638, Japan

[4] Hlth Sci Univ Hokkaido, Sch Nursing & Social Serv, Ishikari, Hokkaido 0610293, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2016年 / 469卷 / 03期

关键词：

HIF-1; alpha; PIAS3; Stabilization; SUMO E3 ligase; Transcriptional regulation; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ACTIVATED STAT3 PIAS3; HISTONE DEACETYLASES; INHIBITOR;

D O I：

10.1016/j.bbrc.2015.12.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-1 alpha. Moreover, PIAS3 overexpression enhanced the transcriptional activity of HIF-1 alpha 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-1 alpha 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-1 alpha-mediated transcription by increasing its protein stability. (C) 2015 Elsevier Inc. All rights reserved.

引用

收藏

页码：470 / 476

页数：7

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