PMID- 26697750
OWN - NLM
STAT- MEDLINE
DCOM- 20160527
LR  - 20160117
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 469
IP  - 3
DP  - 2016 Jan 15
TI  - PIAS3 enhances the transcriptional activity of HIF-1alpha by increasing its protein 
      stability.
PG  - 470-6
LID - S0006-291X(15)31051-2 [pii]
LID - 10.1016/j.bbrc.2015.12.047 [doi]
AB  - 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-1alpha. Moreover, 
      PIAS3 overexpression enhanced the transcriptional activity of HIF-1alpha 
      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-1alpha 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-1alpha-mediated transcription by increasing 
      its protein stability.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Nakagawa, Koji
AU  - Nakagawa K
AD  - Department of Pathophysiology and Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 
      Sapporo, Hokkaido 060-0812, Japan. Electronic address: 
      k_nakagawa@pharm.hokudai.ac.jp.
FAU - Kohara, Toshihisa
AU  - Kohara T
AD  - Department of Gastroenterology and Hematology, Graduate School of Medicine, 
      Hokkaido University, N15 W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
FAU - Uehata, Yasuko
AU  - Uehata Y
AD  - Department of Gastroenterology and Hematology, Graduate School of Medicine, 
      Hokkaido University, N15 W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
FAU - Miyakawa, Yui
AU  - Miyakawa Y
AD  - Department of Pathophysiology and Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 
      Sapporo, Hokkaido 060-0812, Japan.
FAU - Sato-Ueshima, Maremi
AU  - Sato-Ueshima M
AD  - Department of Pathophysiology and Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 
      Sapporo, Hokkaido 060-0812, Japan.
FAU - Okubo, Naoto
AU  - Okubo N
AD  - Department of Pathophysiology and Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 
      Sapporo, Hokkaido 060-0812, Japan.
FAU - Asaka, Masahiro
AU  - Asaka M
AD  - Department of Gastroenterology and Hematology, Graduate School of Medicine, 
      Hokkaido University, N15 W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan; 
      Department of Cancer Preventive Medicine, Graduate School of Medicine, Hokkaido 
      University, N15 W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
FAU - Takeda, Hiroshi
AU  - Takeda H
AD  - Department of Pathophysiology and Therapeutics, Division of Pharmasciences, 
      Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, 
      Sapporo, Hokkaido 060-0812, Japan; Department of Gastroenterology and Hematology, 
      Graduate School of Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo, 
      Hokkaido 060-8638, Japan.
FAU - Kobayashi, Masanobu
AU  - Kobayashi M
AD  - Department of Cancer Preventive Medicine, Graduate School of Medicine, Hokkaido 
      University, N15 W7 Kita-ku, Sapporo, Hokkaido 060-8638, Japan; School of Nursing 
      and Social Services, Health Sciences University of Hokkaido, Ishikari-Toubetsu, 
      Hokkaido 061-0293, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151215
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Molecular Chaperones)
RN  - 0 (PIAS3 protein, human)
RN  - 0 (Protein Inhibitors of Activated STAT)
SB  - IM
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Molecular Chaperones/*metabolism
MH  - Protein Inhibitors of Activated STAT/*metabolism
MH  - Protein Stability
MH  - Signal Transduction/*physiology
MH  - Transcriptional Activation/*physiology
OTO - NOTNLM
OT  - HIF-1alpha
OT  - PIAS3
OT  - SUMO E3 ligase
OT  - Stabilization
OT  - Transcriptional regulation
EDAT- 2015/12/25 06:00
MHDA- 2016/05/28 06:00
CRDT- 2015/12/25 06:00
PHST- 2015/12/02 00:00 [received]
PHST- 2015/12/11 00:00 [accepted]
PHST- 2015/12/25 06:00 [entrez]
PHST- 2015/12/25 06:00 [pubmed]
PHST- 2016/05/28 06:00 [medline]
AID - S0006-291X(15)31051-2 [pii]
AID - 10.1016/j.bbrc.2015.12.047 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Jan 15;469(3):470-6. doi: 
      10.1016/j.bbrc.2015.12.047. Epub 2015 Dec 15.