المؤلفون: 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

المصدر: Ohshiro , K , Rayala , S K , Wigerup , C , Pakala , S B , Natha , R S D , Gururaj , A E , Molli , P R , Månsson , S S , Ramezani , A , Hawley , R G , Landberg , G , Lee , N H & Kumar , R 2010 , ' Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator ' , EMBO reports , vol. 11 , no. 9 , pp. 691-697 . https://doi.org/10.1038/embor.2010.99Test

مصطلحات موضوعية: Lys 626 acetylation, MTA1, Raf1 activation, Ras, transformation

الوصف: 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 ±i2 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 ±i2 regulatory element and consequently for the repression of G ±i2 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. © 2010 European Molecular Biology Organization.

الإتاحة: https://doi.org/10.1038/embor.2010.99Test
https://research.manchester.ac.uk/en/publications/21019312-9fbc-4957-af87-0cf0d03c7a38Test

المؤلفون: 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

المصدر: Pathology Faculty Publications

مصطلحات موضوعية: Lys 626 acetylation, MTA1, Raf1 activation, Ras, transformation

الوصف: 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 ±i2 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 ±i2 regulatory element and consequently for the repression of G ±i2 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. © 2010 European Molecular Biology Organization.

العلاقة: https://hsrc.himmelfarb.gwu.edu/smhs_path_facpubs/1263Test

الإتاحة: https://hsrc.himmelfarb.gwu.edu/smhs_path_facpubs/1263Test

المؤلفون: 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, Göran, Lee, Norman H, Kumar, Rakesh

المساهمون: Department 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.

مصطلحات موضوعية: MTA1, Lys 626 Acetylation, Raf1 Activation, Ras

الوصف: 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.

العلاقة: Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator. 2010, 11 (9):691-7 EMBO Rep; http://hdl.handle.net/10541/112797Test; EMBO Reports

الإتاحة: https://doi.org/10.1038/embor.2010.99Test
http://hdl.handle.net/10541/112797Test