Clusterin, a Novel DEC1 Target, Modulates DNA Damage-Mediated Cell Death

Molecular Cancer Research : MCR
Xin MingYingjuan Qian

Abstract

Differentiated embryonic chondrocyte expressed gene 1 (DEC1, also known as Sharp2/Stra13/BHLHE40) is a basic helix-loop-helix transcription factor that plays an important role in circadian rhythms, cell proliferation, apoptosis, cellular senescence, hypoxia response, and epithelial-to-mesenchymal transition of tumor cells. Secretory clusterin (sCLU) is a cytoprotective protein that guards against genotoxic stresses. Here, clusterin (CLU) was identified as a novel target gene of DEC1 and suppresses DNA damage-induced cell death in tumor cells. Mechanistically, based on chromatin immunoprecipitation and luciferase assays, DEC1 binds to and activates the promoter of the CLU gene. DEC1 and DNA-damaging agents induce sCLU expression, whereas DEC1 knockdown decreases the expression of sCLU upon DNA damage. Moreover, the data demonstrate that DEC1 inhibits, whereas sCLU knockdown enhances, DNA damage-induced cell death in MCF7 breast cancer cells. Given that DEC1 and sCLU are frequently overexpressed in breast cancers, these data provide mechanistic insight into DEC1 as a prosurvival factor by upregulating sCLU to reduce the DNA damage-induced apoptotic response. Together, this study reveals sCLU as a novel target of DEC1 which modula...Continue Reading

References

Jul 1, 1995·The International Journal of Biochemistry & Cell Biology·M E Rosenberg, J Silkensen
Apr 20, 2000·The Journal of Biological Chemistry·M CervelleraA Sala
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·C R YangD A Boothman
Aug 10, 2000·The American Journal of Pathology·M RedondoC K Petito
Mar 22, 2002·The International Journal of Biochemistry & Cell Biology·Steve E Jones, Catherine Jomary
Oct 25, 2002·Nature·Sato HonmaKen-ichi Honma
Jan 29, 2003·The Journal of Biological Chemistry·Konstantin S LeskovDavid A Boothman
Mar 8, 2003·The Journal of Biological Chemistry·Yuxin LiBingfang Yan
Sep 26, 2003·Cancer Biology & Therapy·Tracy CriswellDavid A Boothman
Nov 18, 2003·International Journal of Cancer. Journal International Du Cancer·Maurizio ScaltritiSaverio Bettuzzi
Sep 3, 2004·Cancer Research·Maurizio ScaltritiSaverio Bettuzzi
Jan 15, 2005·Free Radical Biology & Medicine·Ioannis P TrougakosEfstathios S Gonos
Jun 23, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Kazuya Yamada, Kaoru Miyamoto
Aug 23, 2005·Nature Cell Biology·Honglai ZhangCun-Yu Wang
Sep 24, 2005·Cell Death and Differentiation·B ShannanJ Reichrath
Nov 11, 2006·International Journal of Cancer. Journal International Du Cancer·Magda LourdaEfstathios S Gonos
Nov 3, 2009·Advances in Cancer Research·Sabina Pucci, Saverio Bettuzzi
Nov 3, 2009·Advances in Cancer Research·Julie Y Djeu, Sheng Wei
Feb 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amina ZoubeidiMartin Gleave
Aug 25, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kim N ChiElizabeth A Eisenhauer
May 10, 2011·Biochemical and Biophysical Research Communications·Gukhan KimSeung-Whan Kim
Oct 12, 2011·Molecular Cancer Research : MCR·Masaki ShiotaMartin E Gleave
Dec 22, 2011·Journal of Experimental & Clinical Cancer Research : CR·Mohamed K HassanNoriaki Sakuragi
Dec 27, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Janessa J LaskinDesiree Hao
Jun 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yingjuan QianXinbin Chen
Sep 13, 2012·Journal of Experimental & Clinical Cancer Research : CR·Yong TangYingsheng Jiang
Feb 5, 2014·Molecular and Cellular Endocrinology·Ario TakeuchiAmina Zoubeidi
Mar 29, 2014·OncoTargets and Therapy·Tomas Koltai
Aug 28, 2015·Expert Review of Anticancer Therapy·Lateef A Muhammad, Fred Saad

❮ Previous
Next ❯

Citations

Jun 25, 2020·Genes & Cancer·Zsofia KissParamita M Ghosh
Oct 20, 2020·Cellular Oncology (Dordrecht)·Bárbara MatosMargarida Fardilha
Dec 10, 2020·The Journal of Gene Medicine·Yuwan LinPingyi Xu
May 19, 2021·Biochemical Society Transactions·Hannah BollandEster M Hammond
Feb 6, 2022·Journal of Cellular and Molecular Medicine·Yanfei JiaYunshan Wang

❮ 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