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Acetylation‐dependent oncogenic activity of metastasis‐associated protein 1 co‐regulator
Author(s) -
Ohshiro Kazufumi,
Rayala Suresh K,
Wigerup Caroline,
Pakala Suresh B,
Natha Reddy S Divijendra,
Gururaj Anupama E,
Molli Poonam R,
Månsson Sofie Svensson,
Ramezani Ali,
Hawley Robert G,
Landberg Goran,
Lee Norman H,
Kumar Rakesh
Publication year - 2010
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.99
Subject(s) - acetylation , histone deacetylase , regulator , psychological repression , histone , carcinogenesis , hdac4 , cancer research , microbiology and biotechnology , transcription (linguistics) , repressor , chemistry , transcription factor , biology , gene expression , gene , biochemistry , linguistics , philosophy
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 G α i 2 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 G α i 2 regulatory element and consequently for the repression of G α i 2 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.