Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation

被引:40
作者
Beck, Ilse M. [1 ,2 ]
Drebert, Zuzanna J. [1 ]
Hoya-Arias, Ruben [2 ]
Bahar, Ali A. [2 ]
Devos, Michael [5 ]
Clarisse, Dorien [1 ,3 ,4 ]
Desmet, Sofie [3 ,4 ]
Bougarne, Nadia [3 ,4 ]
Ruttens, Bart [7 ,8 ]
Gossye, Valerie [2 ]
Denecker, Geertrui [5 ]
Lievens, Sam [3 ,4 ]
Bracke, Marc [1 ]
Tavernier, Jan [3 ,4 ]
Declercq, Wim [5 ]
Gevaert, Kris [7 ,8 ]
Vanden Berghe, Wim [2 ,6 ]
Haegeman, Guy [2 ]
De Bosscher, Karolien [2 ,3 ,4 ]
机构
[1] Univ Ghent, Dept Radiat Therapy & Expt Canc Res, Lab Expt Canc Res, B-9000 Ghent, Belgium
[2] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA
[3] VIB, Dept Med Prot Res, Cytokine Receptor Lab, Ghent, Belgium
[4] Univ Ghent, Dept Biochem, Cytokine Receptor Lab, B-9000 Ghent, Belgium
[5] Univ Ghent, VIB, Dept Mol Biomed Res, Mol Signaling & Cell Death Unit, B-9000 Ghent, Zwijnaarde, Belgium
[6] Univ Antwerp, Dept Biomed Sci, Lab Prot Chem Prote & Epigenet Signaling PPES, Antwerp, Belgium
[7] VIB, Dept Med Prot Res, Ghent, Belgium
[8] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium
来源
PLOS ONE | 2013年 / 8卷 / 07期
关键词
PROTEASOME INHIBITION LEADS; BETA-CATENIN; MOLECULAR CHAPERONES; RNA ACTIVATOR; CELL-LINE; KAPPA; TRANSCRIPTION; EXPRESSION; CARCINOMA; SURVIVAL;
D O I
10.1371/journal.pone.0069115
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-kappa B-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated I kappa B alpha degradation and NF-kappa B p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA's anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells.
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页数:18
相关论文
共 67 条
[1]   Engrailed-1 negatively regulates β-catenin transcriptional activity by destabilizing β-catenin via a glycogen synthase kinase-3β-independent pathway [J].
Bachar-Dahan, Liora ;
Goltzmann, Janna ;
Yaniv, Abraham ;
Gazit, Arnona .
MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (06) :2572-2580
[2]   Crosstalk in Inflammation: The Interplay of Glucocorticoid Receptor-Based Mechanisms and Kinases and Phosphatases [J].
Beck, Ilse M. E. ;
Vanden Berghe, Wim ;
Vermeulen, Linda ;
Yamamoto, Keith R. ;
Haegeman, Guy ;
De Bosscher, Karolien .
ENDOCRINE REVIEWS, 2009, 30 (07) :830-882
[3]   Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-κB inhibition [J].
Beck, Ilse Me ;
Vanden Berghe, Wim ;
Vermeulen, Linda ;
Bougarne, Nadia ;
Cruyssen, Bert Vander ;
Haegeman, Guy ;
De Bosscher, Karolien .
EMBO JOURNAL, 2008, 27 (12) :1682-1693
[4]   FRA-1 expression level regulates proliferation and invasiveness of breast cancer cells [J].
Belguise, K ;
Kersual, N ;
Galtier, F ;
Chalbos, D .
ONCOGENE, 2005, 24 (08) :1434-1444
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]  
Bush KT, 1997, J BIOL CHEM, V272, P9086
[7]   Glucocorticoid receptor phosphorylation differentially affects target gene expression [J].
Chen, Weiwei ;
Dang, Thoa ;
Blind, Raymond D. ;
Wang, Zhen ;
Cavasotto, Claudio N. ;
Hittelman, Adam B. ;
Rogatsky, Inez ;
Logan, Susan K. ;
Garabedian, Michael J. .
MOLECULAR ENDOCRINOLOGY, 2008, 22 (08) :1754-1766
[8]   Steroid Receptor RNA Activator - A nuclear receptor coregulator with multiple partners: Insights and challenges [J].
Colley, Shane M. ;
Leedman, Peter J. .
BIOCHIMIE, 2011, 93 (11) :1966-1972
[9]   Steroid receptor RNA activator bi-faceted genetic system: Heads or Tails? [J].
Cooper, Charlton ;
Vincett, Daniel ;
Yan, Yi ;
Hamedani, Mohammad K. ;
Myal, Yvonne ;
Leygue, Etienne .
BIOCHIMIE, 2011, 93 (11) :1973-1980
[10]   Glucocorticoids repress NF-κB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell [J].
De Bosscher, K ;
Vanden Berghe, W ;
Vermeulen, L ;
Plaisance, S ;
Boone, E ;
Haegeman, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) :3919-3924