CSN5 isopeptidase activity links COP9 signalosome activation to breast cancer progression

Cancer Research
Adam S AdlerHoward Y Chang

Abstract

CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here, we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers.

References

Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W S PearD Baltimore
Apr 2, 1998·Genes, Chromosomes & Cancer·M TirkkonenO P Kallioniemi
Aug 10, 1999·Nature·W C HahnR A Weinberg
Sep 2, 1999·Nature Genetics·J R PollackP O Brown
Nov 13, 1999·Nature Cell Biology·A C CarranoM Pagano
Nov 13, 1999·Nature Cell Biology·H SutterlütyW Krek
Nov 15, 2001·The Journal of Biological Chemistry·Moon-Kyoung BaeKyu-Won Kim
Sep 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Howard Y ChangPatrick O Brown
Oct 3, 2002·Nature Reviews. Cancer·Stella PelengarisGerard Evan
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jen-Tsan ChiPatrick O Brown
May 10, 2003·Cancer Treatment Reviews·Grzegorz Nalepa, J Wade Harper
May 29, 2003·Molecular Cell·So Young KimWilliam P Tansey
Jan 23, 2004·PLoS Biology·Xavier I AmbroggioRaymond J Deshaies
Apr 15, 2004·Genes & Development·Lynne BemisWayne Zundel
Aug 10, 2004·The Journal of Biological Chemistry·Kiichiro TomodaJun-Ya Kato
Jan 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Andrew SlackJason M Shohet
Feb 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Howard Y ChangMarc J van de Vijver
Mar 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Alana L WelmJ Michael Bishop
Jul 23, 2005·Neoplasia : an International Journal for Oncology Research·Murali D BashyamJonathan R Pollack
Dec 29, 2005·Molecular Cancer Research : MCR·Katharine S Richardson, Wayne Zundel
Feb 17, 2006·Genes & Development·Timothy C Hallstrom, Joseph R Nevins
Mar 7, 2006·Nature Genetics·Adam S AdlerHoward Y Chang
Oct 10, 2006·FEBS Letters·Akihisa FukumotoJun-ya Kato
Feb 24, 2007·The EMBO Journal·Katrin SchweitzerMichael Naumann
Sep 19, 2007·Cancer Research·Jacques LapointeJonathan R Pollack

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Citations

Mar 20, 2010·Nature Reviews. Cancer·Carlos López-Otín, Tony Hunter
Jun 8, 2012·Nature Reviews. Cancer·Jean-Christophe Marine
Oct 15, 2011·Oncogene·J M FraileC López-Otín
Jan 26, 2011·The Cancer Journal·Rafael RosellJose Miguel Sanchez
Oct 20, 2010·Cell Division·Terry J Shackleford, Francois X Claret
Jun 7, 2008·Breast Cancer Research : BCR·Jiaxu WangPeter H Watson
Jun 22, 2011·Breast Cancer Research : BCR·Terry J ShacklefordFrancois X Claret
Feb 2, 2011·PloS One·Chiara LuiseStefano Confalonieri
Jun 7, 2012·FEBS Letters·Anke K SchützJürgen Bernhagen
Feb 19, 2013·Biochemical and Biophysical Research Communications·Gui-Ping XuJian-Hua Tong
May 18, 2010·Pulmonary Pharmacology & Therapeutics·Rafael RosellMiquel Taron
Jan 24, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Martina PanattoniRuggero Pardi
Oct 13, 2015·Cell Reports·Shelly RozenMichal Sharon
Mar 31, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Angela CiriglianoTeresa Rinaldi
Feb 6, 2014·Cancer Biology & Therapy·Yunbao PanFrancois X Claret
Aug 31, 2011·Cell Cycle·Mong-Hong LeeSai-Ching J Yeung
Jul 15, 2016·Medical Oncology·Lin WangDong-Sheng Pei
Jan 15, 2014·Molecular and Cellular Biology·Maria G Füzesi-LeviMichal Sharon
May 22, 2013·The Journal of Biological Chemistry·Cheng LiuNing Wei
Jan 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaoli HuXueqiong Zhu
Jan 18, 2020·Journal of Proteome Research·Jingzi ZhangLei Fang

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