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dc.contributor.authorOhshiro, Kazufumi
dc.contributor.authorRayala, Suresh K
dc.contributor.authorWigerup, Caroline
dc.contributor.authorPakala, Suresh B
dc.contributor.authorNatha, Reddy S Divijendra
dc.contributor.authorGururaj, Anupama E
dc.contributor.authorMolli, Poonam R
dc.contributor.authorMånsson, Sofie Svensson
dc.contributor.authorRamezani, Ali
dc.contributor.authorHawley, Robert G
dc.contributor.authorLandberg, Göran
dc.contributor.authorLee, Norman H
dc.contributor.authorKumar, Rakesh
dc.date.accessioned2010-10-12T11:25:38Z
dc.date.available2010-10-12T11:25:38Z
dc.date.issued2010-09
dc.identifier.citationAcetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator. 2010, 11 (9):691-7 EMBO Repen
dc.identifier.issn1469-3178
dc.identifier.pmid20651739
dc.identifier.doi10.1038/embor.2010.99
dc.identifier.urihttp://hdl.handle.net/10541/112797
dc.description.abstractHigh 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.
dc.language.isoenen
dc.subjectMTA1en
dc.subjectLys 626 Acetylationen
dc.subjectRaf1 Activationen
dc.subjectRasen
dc.titleAcetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry and Molecular Biology and Institute of Coregulator Biology, The George Washington University Medical Center, 2300 I Street Northwest, Washington, District of Columbia 20037, USA.en
dc.identifier.journalEMBO Reportsen
refterms.dateFOA2020-05-01T14:49:29Z
html.description.abstractHigh 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.


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