The Tumor Suppressor CIC Directly Regulates MAPK Pathway Genes via Histone Deacetylation.

Cancer Research
Simon WeissmannK Helin

Abstract

Oligodendrogliomas are brain tumors accounting for approximately 10% of all central nervous system cancers. CIC is a transcription factor that is mutated in most patients with oligodendrogliomas; these mutations are believed to be a key oncogenic event in such cancers. Analysis of the Drosophila melanogaster ortholog of CIC, Capicua, indicates that CIC loss phenocopies activation of the EGFR/RAS/MAPK pathway, and studies in mammalian cells have demonstrated a role for CIC in repressing the transcription of the PEA3 subfamily of ETS transcription factors. Here, we address the mechanism by which CIC represses transcription and assess the functional consequences of CIC inactivation. Genome-wide binding patterns of CIC in several cell types revealed that CIC target genes were enriched for MAPK effector genes involved in cell-cycle regulation and proliferation. CIC binding to target genes was abolished by high MAPK activity, which led to their transcriptional activation. CIC interacted with the SIN3 deacetylation complex and, based on our results, we suggest that CIC functions as a transcriptional repressor through the recruitment of histone deacetylases. Independent single amino acid substitutions found in oligodendrogliomas preven...Continue Reading

References

May 23, 2001·Nature Neuroscience·L ContiE Cattaneo
Apr 30, 2003·Nature Cell Biology·Atsuo SasakiAkihiko Yoshimura
Jun 3, 2004·Nature Reviews. Molecular Cell Biology·Hong Joo Kim, Dafna Bar-Sagi
May 5, 2005·Oncogene·Lorenzo MagrassiElena Cattaneo
Aug 10, 2005·PLoS Biology·Luciano ContiAustin Smith
Jan 27, 2007·The EMBO Journal·Sergio AstigarragaGerardo Jiménez
May 24, 2008·Nature·Qi-Long YingAustin Smith
Apr 14, 2011·Bioinformatics·Philip Machanick, Timothy L Bailey
Aug 6, 2011·Science·Chetan BettegowdaKenneth W Kinzler
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Apr 25, 2012·Journal of Cell Science·Gerardo JiménezZe'ev Paroush
Jul 21, 2012·The FEBS Journal·Christopher J Caunt, Stephen M Keyse
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Jan 21, 2014·Nature Reviews. Cancer·Anna LasorellaAntonio Iavarone
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 9, 2015·PLoS Genetics·Marta ForésGerardo Jiménez
Apr 8, 2015·Nature Genetics·Hiromichi SuzukiSeishi Ogawa
May 29, 2015·Annals of Neurology·Vincent GleizeMarc Sanson
Jun 11, 2015·The New England Journal of Medicine·UNKNOWN Cancer Genome Atlas Research NetworkJianan Zhang
Sep 12, 2015·Genes, Chromosomes & Cancer·Vijay PadulNeelam Vishwanath Shirsat
Mar 2, 2016·Nature Structural & Molecular Biology·Mads LerdrupKlaus Hansen
Sep 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·Liu YangAlexey Veraksa
Nov 22, 2016·Nature Genetics·Ross A OkimotoTrever G Bivona
Feb 9, 2017·Genes & Development·Sida LiaoStephen J Elledge
Aug 23, 2017·Genes & Development·Lucía Simón-CarrascoMariano Barbacid
Sep 28, 2017·Developmental Cell·Justine PascualFisun Hamaratoglu
Feb 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Qiumin TanHuda Y Zoghbi

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Citations

Apr 3, 2020·Experimental & Molecular Medicine·Yoontae Lee
Aug 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yone Kawe LinRoss A Okimoto
Feb 12, 2020·Cancer Cell International·Jeon-Soo LeeYoontae Lee
Feb 28, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sungjun ParkYoontae Lee
Jun 25, 2019·Frontiers in Cell and Developmental Biology·Kirti SnigdhaMadhuri Kango-Singh
Apr 2, 2020·JCI Insight·Inah HwangJihye Paik
Nov 21, 2020·Annals of Surgical Oncology·Shohei YoshiyaMasaki Mori
Oct 27, 2020·IScience·Yibo RenYongping Shao
Mar 27, 2021·Nature Communications·Ana Martinez-ValJavier Munoz
Apr 18, 2021·Trends in Molecular Medicine·Anna KarpukhinaYegor S Vassetzky
Jun 5, 2021·Scientific Reports·Brenna HouriganQiumin Tan
Jun 25, 2021·Current Biology : CB·Aleena L PatelStanislav Y Shvartsman
Jun 25, 2021·Disease Models & Mechanisms·Thomas P ZwakaMarion Dejosez
Sep 28, 2021·Journal of Neuro-oncology·Débora Cabral de Carvalho CorrêaSilvia Regina Caminada de Toledo
Sep 17, 2021·The British Journal of Dermatology·M Z X XiaoR Gniadecki

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