TG2 regulates the heat-shock response by the post-translational modification of HSF1

EMBO Reports
Federica RossinMauro Piacentini

Abstract

Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response.

References

Feb 11, 1990·Journal of Neurochemistry·T S NowakM J Schlesinger
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·Y YangJ M Wilson
Dec 29, 1998·The Journal of Cell Biology·J A JohnstonR R Kopito
Jan 29, 1999·Physiological Reviews·R R Kopito
Mar 17, 1999·The EMBO Journal·G C MeachamD M Cyr
Dec 13, 2000·Molecular and Cellular Biology·V De Laurenzi, G Melino
May 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L PirkkalaL Sistonen
Oct 9, 2002·Trends in Biochemical Sciences·Laszlo Fesus, Mauro Piacentini
Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Laszlo Lorand, Robert M Graham
Sep 27, 2005·Journal of Neurochemistry·Jeremy M Van RaamsdonkBlair R Leavitt
Nov 18, 2005·Molecular Genetics and Genomics : MGG·Yukiko TakemoriHiroshi Sakurai
Sep 19, 2006·Biochimica Et Biophysica Acta·Pier Giorgio MastroberardinoMauro Piacentini
Jun 22, 2007·Pharmacology & Therapeutics·Matthew Siegel, Chaitan Khosla
Nov 14, 2008·Journal of Cellular Physiology·Zhen-Xian DuHua-Qin Wang
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Dec 4, 2009·Autophagy·Manuela D'ElettoMauro Piacentini
Jun 16, 2010·The Journal of Biological Chemistry·Jorunn StamnaesLudvig M Sollid
Jun 24, 2010·Journal of Neurochemistry·Mélanie BousquetFrancesca Cicchetti
Jul 16, 2010·Nature Reviews. Molecular Cell Biology·Malin AkerfeltLea Sistonen
Jul 29, 2010·EMBO Molecular Medicine·Stephen J McConougheyRajiv R Ratan
Oct 15, 2010·The FEBS Journal·Mitsuaki Fujimoto, Akira Nakai
Oct 23, 2010·Journal of Internal Medicine·P G Mastroberardino, M Piacentini
Jan 1, 2010·Signal Transduction Insights·S K CalderwoodY Zhang
Aug 20, 2011·PloS One·Lonneke HeldensNicolette H Lubsen
Oct 22, 2011·Biochimica Et Biophysica Acta·Soner GundemirGail V W Johnson
Feb 11, 2012·Cell Death and Differentiation·M D'ElettoM Piacentini
Mar 1, 2012·International Review of Cell and Molecular Biology·Maria V Nurminskaya, Alexey M Belkin
Jan 21, 2014·Cellular and Molecular Life Sciences : CMLS·Giorgio CozzaLorenzo A Pinna

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Citations

Jan 30, 2019·Medical Sciences : Open Access Journal·Claudio TabolacciSimone Beninati
Mar 16, 2019·Cell Death & Disease·Valeria R VillellaLuigi Maiuri
Jul 11, 2019·The FEBS Journal·Maria Luisa Di PaoloAnna Minarini
Dec 1, 2018·The EMBO Journal·Valeria R VillellaLuigi Maiuri
Mar 10, 2020·The FEBS Journal·Jarvier N MohammedJerry E Chipuk
Jun 17, 2018·Biological Chemistry·Manuela D'ElettoMauro Piacentini
Mar 23, 2019·Italian Journal of Pediatrics·Luigi MaiuriGuido Kroemer
Feb 10, 2019·Cell Death & Disease·Luigi MaiuriGuido Kroemer
Feb 23, 2019·Molecular & Cellular Oncology·Lorenzo Galluzzi, Guido Kroemer
Mar 7, 2021·Cell Death & Disease·Federica RossinLuigi Leanza
May 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Luca OcchigrossiMauro Piacentini
Jul 3, 2021·International Journal of Molecular Sciences·Luca OcchigrossiFederica Rossin
Jul 18, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Bingwei ZhangKe Tan
Aug 31, 2021·The EMBO Journal·Daniel J KlionskyFederico Pietrocola

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