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Title: Requirement of Hsp105 in CoCl{sub 2}-induced HIF-1α accumulation and transcriptional activation

Abstract

The mammalian stress protein Hsp105α protects cells from stress conditions. Several studies have indicated that Hsp105α is overexpressed in many types of solid tumors, which contain hypoxic microenvironments. However, the role of Hsp105α in hypoxic tumors remains largely unknown. We herein demonstrated the involvement of Hsp105α in HIF-1 functions induced by the hypoxia-mimetic agent CoCl{sub 2}. While Hsp105α is mainly localized in the cytoplasm under normal conditions, a treatment with CoCl{sub 2} induces the nuclear localization of Hsp105α, which correlated with HIF-1α expression levels. The overexpression of degradation-resistant HIF-1α enhances the nuclear localization of Hsp105α without the CoCl{sub 2} treatment. The CoCl{sub 2}-dependent transcriptional activation of HIF-1, which is measured using a reporter gene containing a HIF-responsive element, is reduced by the knockdown of Hsp105α. Furthermore, the CoCl{sub 2}-induced accumulation of HIF-1α is enhanced by heat shock, which results in the nuclear localization of Hsp105, and is suppressed by the knockdown of Hsp105. Hsp105 associates with HIF-1α in CoCl{sub 2}-treated cells. These results suggest that Hsp105α plays an important role in the functions of HIF-1 under hypoxic conditions, in which Hsp105α enhances the accumulation and transcriptional activity of HIF-1 through the HIF-1α-mediated nuclear localization of Hsp105α. - Highlights: • Hsp105αmore » is required for the CoCl{sub 2}-induced transcriptional activation and accumulation of HIF-1. • Hsp105α localizes to the nucleus and interacts with HIF-1α in CoCl{sub 2}-treated cells. • Hsp105 enhances the CoCl{sub 2}-induced accumulation of HIF-1α under heat shock conditions.« less

Authors:
; ; ; ; ;
Publication Date:
OSTI Identifier:
22649834
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 352; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; BUILDUP; COBALT CHLORIDES; CYTOPLASM; GENES; HEAT; NEOPLASMS; PROTEINS

Citation Formats

Mikami, Hiroki, Saito, Youhei, E-mail: ysaito@mb.kyoto-phu.ac.jp, Okamoto, Namiko, Kakihana, Ayana, Kuga, Takahisa, and Nakayama, Yuji, E-mail: nakayama@mb.kyoto-phu.ac.jp. Requirement of Hsp105 in CoCl{sub 2}-induced HIF-1α accumulation and transcriptional activation. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.02.004.
Mikami, Hiroki, Saito, Youhei, E-mail: ysaito@mb.kyoto-phu.ac.jp, Okamoto, Namiko, Kakihana, Ayana, Kuga, Takahisa, & Nakayama, Yuji, E-mail: nakayama@mb.kyoto-phu.ac.jp. Requirement of Hsp105 in CoCl{sub 2}-induced HIF-1α accumulation and transcriptional activation. United States. doi:10.1016/J.YEXCR.2017.02.004.
Mikami, Hiroki, Saito, Youhei, E-mail: ysaito@mb.kyoto-phu.ac.jp, Okamoto, Namiko, Kakihana, Ayana, Kuga, Takahisa, and Nakayama, Yuji, E-mail: nakayama@mb.kyoto-phu.ac.jp. Wed . "Requirement of Hsp105 in CoCl{sub 2}-induced HIF-1α accumulation and transcriptional activation". United States. doi:10.1016/J.YEXCR.2017.02.004.
@article{osti_22649834,
title = {Requirement of Hsp105 in CoCl{sub 2}-induced HIF-1α accumulation and transcriptional activation},
author = {Mikami, Hiroki and Saito, Youhei, E-mail: ysaito@mb.kyoto-phu.ac.jp and Okamoto, Namiko and Kakihana, Ayana and Kuga, Takahisa and Nakayama, Yuji, E-mail: nakayama@mb.kyoto-phu.ac.jp},
abstractNote = {The mammalian stress protein Hsp105α protects cells from stress conditions. Several studies have indicated that Hsp105α is overexpressed in many types of solid tumors, which contain hypoxic microenvironments. However, the role of Hsp105α in hypoxic tumors remains largely unknown. We herein demonstrated the involvement of Hsp105α in HIF-1 functions induced by the hypoxia-mimetic agent CoCl{sub 2}. While Hsp105α is mainly localized in the cytoplasm under normal conditions, a treatment with CoCl{sub 2} induces the nuclear localization of Hsp105α, which correlated with HIF-1α expression levels. The overexpression of degradation-resistant HIF-1α enhances the nuclear localization of Hsp105α without the CoCl{sub 2} treatment. The CoCl{sub 2}-dependent transcriptional activation of HIF-1, which is measured using a reporter gene containing a HIF-responsive element, is reduced by the knockdown of Hsp105α. Furthermore, the CoCl{sub 2}-induced accumulation of HIF-1α is enhanced by heat shock, which results in the nuclear localization of Hsp105, and is suppressed by the knockdown of Hsp105. Hsp105 associates with HIF-1α in CoCl{sub 2}-treated cells. These results suggest that Hsp105α plays an important role in the functions of HIF-1 under hypoxic conditions, in which Hsp105α enhances the accumulation and transcriptional activity of HIF-1 through the HIF-1α-mediated nuclear localization of Hsp105α. - Highlights: • Hsp105α is required for the CoCl{sub 2}-induced transcriptional activation and accumulation of HIF-1. • Hsp105α localizes to the nucleus and interacts with HIF-1α in CoCl{sub 2}-treated cells. • Hsp105 enhances the CoCl{sub 2}-induced accumulation of HIF-1α under heat shock conditions.},
doi = {10.1016/J.YEXCR.2017.02.004},
journal = {Experimental Cell Research},
number = 2,
volume = 352,
place = {United States},
year = {Wed Mar 15 00:00:00 EDT 2017},
month = {Wed Mar 15 00:00:00 EDT 2017}
}