KMT Set7/9 affects genotoxic stress response via the Mdm2 axis

Oncotarget
Larissa LezinaNikolai A Barlev

Abstract

Genotoxic stress inflicted by anti-cancer drugs causes DNA breaks and genome instability. DNA double strand breaks induced by irradiation or pharmacological inhibition of Topoisomerase II activate ATM (ataxia-telangiectasia-mutated) kinase signalling pathway that in turn triggers cell cycle arrest and DNA repair. ATM-dependent gamma-phosphorylation of histone H2Ax and other histone modifications, including ubiquitnylation, promote exchange of histones and recruitment of DNA damage response (DDR) and repair proteins. Signal transduction pathways, besides DDR itself, also control expression of genes whose products cause cell cycle arrest and/or apoptosis thus ultimately affecting the sensitivity of cells to genotoxic stress. In this study, using a number of experimental approaches we provide evidence that lysine-specific methyltransferase (KMT) Set7/9 affects DDR and DNA repair, at least in part, by regulating the expression of an E3 ubiquitin ligase, Mdm2. Furthermore, we show that Set7/9 physically interacts with Mdm2. Several cancer cell lines with inverse expression of Set7/9 and Mdm2 displayed diminished survival in response to genotoxic stress. These findings are signified by our bioinformatics studies suggesting that the u...Continue Reading

References

Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Mar 15, 2001·Current Opinion in Cell Biology·D Durocher, S P Jackson
Aug 2, 2002·The Journal of Biological Chemistry·Aaron W AdamsonKevin D Brown
Nov 7, 2002·Current Biology : CB·Junya KobayashiKenshi Komatsu
May 27, 2003·Nature Cell Biology·Natalia PediconiMassimo Levrero
Apr 22, 2004·Molecular Cell·Antigone KouskoutiIannis Talianidis
Nov 5, 2004·Nature·Sergei ChuikovDanny Reinberg
Dec 3, 2005·Cancer Research·Shahnaz T Al RashidRobert G Bristow
May 23, 2006·Current Cancer Drug Targets·J KaoS J Kron
Jun 9, 2006·Cell Cycle·Anna Morgunkova, Nick A Barlev
Apr 5, 2007·Nature Protocols·Peggy L Olive, Judit P Banáth
Jul 25, 2007·Molecular and Cellular Biology·Gleb S IvanovNickolai A Barlev
Feb 21, 2008·Nature Reviews. Molecular Cell Biology·Dana Branzei, Marco Foiani
May 13, 2008·Molecular Cell·Krithika SubramanianPaula M Vertino
Jun 11, 2008·Molecular and Cellular Biology·Alyssa BouskaChristine M Eischen
Apr 9, 2009·Biochemical and Biophysical Research Communications·Toshihiro Masatsugu, Ken Yamamoto
Oct 23, 2009·Nature·Stephen P Jackson, Jiri Bartek
Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Chee-Kwee Ea, David Baltimore
Feb 18, 2010·Cell Cycle·Yingli SunBrendan D Price
Mar 20, 2010·Trends in Cell Biology·Anthony L Forget, Stephen C Kowalczykowski
Jul 7, 2010·Molecular Cell·Haroula Kontaki, Iannis Talianidis
Oct 21, 2010·Nucleic Acids Research·Luke GaughanCraig N Robson
Nov 3, 2010·DNA Repair·Simon Bekker-Jensen, Niels Mailand
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jinbo YangGeorge R Stark
Jan 29, 2011·Molecular Endocrinology·Soyoung KoBandana Chatterjee
Feb 16, 2011·Journal of Receptor and Signal Transduction Research·Qi XieZengqiang Yuan
Jun 28, 2011·Nature Structural & Molecular Biology·Jiaxue WuXiaochun Yu
Aug 23, 2011·Molecular Cell·Bernhard LehnertzFabio M V Rossi
Sep 9, 2011·Cell Cycle·Jeffrey V WongLingchong You
Oct 27, 2011·Seminars in Cell & Developmental Biology·Torben R Kasparek, Timothy C Humphrey
Dec 20, 2011·Cancer Research·Anup K Biswas, David G Johnson
Sep 18, 2012·Cell·Francesca MattiroliTitia K Sixma
Nov 15, 2012·Genes & Cancer·Maurisa F Riley, Guillermina Lozano
Dec 12, 2012·Trends in Molecular Medicine·Brigitte M Pützer, David Engelmann
Jan 19, 2013·Journal of Molecular Cell Biology·Kuei-Yang Hsiao, Craig A Mizzen

❮ Previous
Next ❯

Citations

Jul 23, 2016·Oncotarget·Alberto MariniGerry Melino
Nov 21, 2018·Cell Death Discovery·Emil BulatovNickolai A Barlev
Jan 19, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yongchun SongYu Yao
Jun 1, 2018·Cell Biology International·Alexander ErmakovNickolai A Barlev
Jan 2, 2018·Oncotarget·Miran RadaSalvador Macip
Oct 17, 2017·Oncotarget·Palaniraja ThandapaniStéphane Richard
Nov 21, 2018·Oncogene·Olga FedorovaNikolai A Barlev
Apr 26, 2020·Pathogens·Sergei N BorchseniusNikolai A Barlev
Aug 28, 2018·Journal of Cellular Physiology·Sergey N BorchseniusNickolai A Barlev
Oct 22, 2020·Cell Death Discovery·Olga FedorovaNikolai Barlev
Sep 24, 2019·Chemico-biological Interactions·Alina HanfAndreas Daiber
Dec 15, 2020·Cell Death & Disease·Oleg ShuvalovNikolai Barlev
Aug 4, 2021·Biochemical and Biophysical Research Communications·Alexandra DaksNickolai Barlev

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
flow cytometry
transfection
PCR

Software Mentioned

Operetta
Cell Quest Pro
Modfit
R
CometScore

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis