DUSP1 is controlled by p53 during the cellular response to oxidative stress

Molecular Cancer Research : MCR
Yu-Xin LiuYuxin Yin

Abstract

p53 controls the cellular response to genotoxic stress through multiple mechanisms. We report here that p53 regulates DUSP1, a dual-specific threonine and tyrosine phosphatase with stringent substrate specificity for mitogen-activated protein kinase (MAPK). DUSP1 is a potent inhibitor of MAPK activity through dephosphorylation of MAPK. In a colon cancer cell line containing inducible ectopic p53, DUSP1 protein level is significantly increased upon activation of p53, leading to cell death in response to nutritional stress. In mouse embryo fibroblast cells, DUSP1 protein abundance is greatly increased after oxidative stress in a p53-dependent manner and also when apoptosis is triggered. We show that p53 induces the activity of a human DUSP1 regulatory region. Furthermore, p53 can physically interact with the DUSP1 regulatory region in vivo, and p53 binds to a 10-bp perfect palindromic site in this DUSP1 regulatory region. We show that overexpression of DUSP1 or inhibition of MAPK activity significantly increases cellular susceptibility to oxidative damage. These findings indicate that p53 is a transcriptional regulator of DUSP1 in stress responses. Our results reveal a mechanism whereby p53 selectively regulates target genes and ...Continue Reading

References

Apr 1, 1992·Nature Genetics·W S el-DeiryB Vogelstein
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P ShawJ Costa
Feb 1, 1995·Japanese Journal of Cancer Research : Gann·K NoguchiT Tsuruo
Jan 1, 1993·Advances in Experimental Medicine and Biology·M B Kastan
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 16, 1993·Nature·Y XiongD Beach
Apr 1, 1996·The Journal of Cell Biology·R P HuangE D Adamson
Sep 26, 1997·Nature·K PolyakB Vogelstein
Dec 1, 2000·Nature·B VogelsteinA J Levine
Jul 21, 2001·Molecular Cell·J YuB Vogelstein
Jul 21, 2001·Molecular Cell·K Nakano, K H Vousden
Aug 2, 2003·The Journal of Biological Chemistry·Maoxiang LiGen Sheng Wu
Nov 13, 2003·Molecular and Cellular Biology·Salvador MacipStuart A Aaronson
Oct 20, 2006·Molecular Cancer Research : MCR·Y Jenny JinYuxin Yin

❮ Previous
Next ❯

Citations

Sep 10, 2011·Journal of Neural Transmission·Bokyung ParkYoung J Oh
Jan 30, 2010·Cancer Metastasis Reviews·Kelly K Haagenson, Gen Sheng Wu
Nov 15, 2012·Molecular and Cellular Biology·Izumi KatoHiroyoshi Ariga
Jan 26, 2010·BMC Molecular Biology·Emmanuelle WilhelmBrendan Bell
Nov 19, 2013·PLoS Pathogens·Ana CáceresMariano Esteban
Feb 5, 2014·Clinical & Experimental Metastasis·Hassan Fazilaty, Parvin Mehdipour
Jan 25, 2011·Journal of Signal Transduction·Wayne ChadwickStuart Maudsley
Feb 18, 2009·BJU International·Christopher C UzohRaj A Persad
Mar 3, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Maria Lauda TomasiShelly C Lu
Dec 9, 2014·Cell Cycle·Martin FischerKurt Engeland
Jun 19, 2015·PLoS Genetics·Jörg BartelFabian J Theis
Jul 17, 2016·Biochemical and Biophysical Research Communications·Yu-Seon KangJang-Seong Kim
Aug 1, 2016·Computational Biology and Chemistry·Mousumi Sahu, Bibekanand Mallick
Apr 6, 2017·Scientific Reports·Krithika LingappanBhagavatula Moorthy
Dec 19, 2017·The Journal of International Medical Research·Huong Duong-Thi-LySy Duong-Quy
Jul 18, 2017·Antioxidants & Redox Signaling·David D RobertsJeffrey S Isenberg
Oct 12, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Regina TrollmannMax Gassmann
Aug 20, 2017·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Bradley N MillsMarc W Halterman
Mar 12, 2019·Cell Death Discovery·Fabiana V MelloAlberto Orfao
Aug 11, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mercedes TaroncherMaría-José Ruiz

❮ Previous
Next ❯

Related Concepts

Related Feeds

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