Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator.

EMBO Reports
Kazufumi OhshiroRakesh Kumar

Abstract

High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of Galphai2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the Galphai2 regulatory element and consequently for the repression of Galphai2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time--to the best of our knowledge--evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product.

References

Oct 29, 2002·Nature Cell Biology·Hiroshi HanafusaEisuke Nishida
Nov 13, 2003·Seminars in Oncology·Rakesh KumarRozita Bagheri-Yarmand
Aug 16, 2005·Cancer Cell·Madhu MacraeFrank McCormick
Sep 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xiao-Yong ZhangSteven B McMahon
Apr 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Anupama E GururajRakesh Kumar
Dec 5, 2006·The Journal of Biological Chemistry·Bramanandam Manavathi, Rakesh Kumar
Aug 3, 2007·Cancer Research·Seetharaman BalasenthilRakesh Kumar

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Citations

Jul 8, 2011·Nature Reviews. Cancer·Anne Y Lai, Paul A Wade
Oct 22, 2014·Cancer Metastasis Reviews·Anait S LevensonXu Zhang
Oct 27, 2014·Cancer Metastasis Reviews·Nirmalya SenRakesh Kumar
Nov 7, 2014·Cancer Metastasis Reviews·Ekjot KaurShilpee Dutt
Oct 22, 2014·Cancer Metastasis Reviews·Yun Zhang, Xiao-Fan Wang
Oct 19, 2014·Cancer Metastasis Reviews·Soo Hyung RyuYoung-Hwa Chung
Oct 25, 2014·Cancer Metastasis Reviews·Zhifeng NingHao Zhang
Feb 13, 2016·Gene·Rakesh Kumar, Rui-An Wang
Apr 14, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sujit S NairRakesh Kumar
Jul 5, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sujit S NairRakesh Kumar
Apr 8, 2016·Frontiers of Medicine·Chunxiao LiQimin Zhan
Jan 13, 2015·Journal of Cellular Physiology·Patrick M LongDiane M Jaworski
Jul 15, 2015·Biochemical and Biophysical Research Communications·Kazufumi Ohshiro, Rakesh Kumar
Nov 25, 2014·Medical Oncology·Taize YuanXiuping Zhang
Apr 13, 2013·Cancer Research·Suresh B PakalaRakesh Kumar
Oct 2, 2019·Biochemical and Biophysical Research Communications·Rohith Kumar GuddetiSuresh B Pakala

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