المؤلفون: Reddy, Sirigiri Divijendra Natha, Rayala, Suresh K., Ohshiro, Kazufumi, Pakala, Suresh B., Kobori, Nobuhide, Dash, Pramod, Yun, Sung, Qin, Jun, O'Malley, Bert W., Kumar, Rakesh

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2011 Mar 01. 108(10), 4200-4205.

الوصول الحر: https://www.jstor.org/stable/41061084Test

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, 1963, Lee, Norman H, Kumar, Rakesh

المصدر: EMBO reports. 11(9):691-7

مصطلحات موضوعية: Cell and Molecular Biology, Cell- och molekylärbiologi, Acetylation, Animals, Cell Line, Cell Movement, Cell Transformation, Neoplastic, Female, Fibroblasts, cytology, physiology, GTP-Binding Protein alpha Subunit, Gi2, genetics, metabolism, Gene Expression Regulation, Histone Deacetylases, Humans, Lysine, Mice, Nude, Neoplasms, Experimental, Oncogenes, Repressor Proteins, Transcription, Genetic, Transplantation, Heterologous, ras Proteins

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.

الوصول الحر: https://gup.ub.gu.se/publication/150800Test

المؤلفون: Li, Da Qiang, Reddy, Sirigiri Divijendra Natha, Pakala, Suresh B., Wu, Xifeng, Zhang, Yanping, Rayala, Suresh K., Kumar, Rakesh

المصدر: The Journal of Biological Chemistry, 284(50)

مصطلحات موضوعية: Mice, Knockout, DNA Repair, Fibroblasts, DNA Damage, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53, Transcription Factors, Humans, Animals, Recombinant Fusion Proteins, Nuclear Proteins, Cell Line, Tumor, Cells, Cultured

الوصف: Although metastasis-associated protein 1 (MTA1) has recently been shown as a DNA damage responsive protein, the underlying mechanism for its role in DNA double-strand break (DSB) repair remains unknown. Here, we show that MTA1 controls p53 stability through inhibiting its ubiquitination by E3 ubiquitin ligases mouse double minute 2 (Mdm2) and constitutive photomorphogenic protein 1 (COP1). The underlying mechanisms involve the ability of MTA1 to compete with COP1 to bind to p53 and/or to destabilize COP1 and Mdm2. Consequently, MTA1 regulates the p53-dependent transcription of p53R2, a direct p53 target gene for supplying nucleotides to repair damaged DNA. Depletion of MTA1 impairs p53-dependent p53R2 transcription and compromises DNA repair. Interestingly, these events could be reversed by MTA1 reintroduction, indicating that MTA1 interjects into the p53-dependent DNA repair. Given the fact that MTA1 is widely up-regulated in human cancers, these findings in conjunction with our earlier finding of a crucial role of MTA1 in DSB repair suggest an inherent role of the MTA1-p53-p53R2 pathway in DNA damage response in cancer cells.

العلاقة: https://doi.org/10.17615/8171-3735Test; https://cdr.lib.unc.edu/downloads/xs55mm53k?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/xs55mm53kTest

الإتاحة: https://doi.org/10.17615/8171-3735Test
https://cdr.lib.unc.edu/downloads/xs55mm53k?file=thumbnailTest
https://cdr.lib.unc.edu/downloads/xs55mm53kTest

المؤلفون: Sankaran, Deivendran, Pakala, Suresh B., Nair, Vasudha S., Sirigiri, Divijendra Natha Reddy, Cyanam, Dinesh, Ha, Ngoc-Han, Li, Da-Qiang, Santhoshkumar, T. R., Pillai, M. Radhakrishna, Kumar, Rakesh

المصدر: The Journal of biological chemistry. 287(8)

مصطلحات موضوعية: Extracellular Matrix Proteins, Transcription, Genetic, JNK Mitogen-Activated Protein Kinases, Molecular Bases of Disease, Breast Neoplasms, Histone Deacetylases, Gene Expression Regulation, Neoplastic, Repressor Proteins, Mice, Carcinoma, Intraductal, Noninfiltrating, Hyaluronan Receptors, Cell Movement, Cell Line, Tumor, Trans-Activators, Animals, Humans, Female, Neoplasm Invasiveness, Additions and Corrections, RNA Polymerase II

الوصف: Even though the hyaluronan-mediated motility receptor (HMMR), a cell surface oncogenic protein, is widely up-regulated in human cancers and correlates well with cell motility and invasion, the underlying molecular and nature of its putative upstream regulation remain unknown. Here, we found for the first time that MTA1 (metastatic tumor antigen 1), a master chromatin modifier, regulates the expression of HMMR and, consequently, its function in breast cancer cell motility and invasiveness. We recognized a positive correlation between the levels of MTA1 and HMMR in human cancer. Furthermore, MTA1 is required for optimal expression of HMMR. The underlying mechanism includes interaction of the MTA1·RNA polymerase II·c-Jun coactivator complex with the HMMR promoter to stimulates its transcription. Accordingly, selective siRNA-mediated knockdown of HMMR in breast cancer cells substantially reduces the invasion and migration of cells. These findings reveal a regulatory role for MTA1 as an upstream coactivator of HMMR expression and resulting biological phenotypes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::f09906911bce6a41dfc5918e6341a610Test
https://pubmed.ncbi.nlm.nih.gov/24014614Test