Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression
| العنوان: | Prohibitin co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression |
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| المؤلفون: | Srikumar Chellappan, Gina Fusaro, Jaya Padmanabhan, Sheng Wang |
| المصدر: | Oncogene. 21:8388-8396 |
| بيانات النشر: | Springer Science and Business Media LLC, 2002. |
| سنة النشر: | 2002 |
| مصطلحات موضوعية: | Cancer Research, Transcription, Genetic, Breast Neoplasms, Histone Deacetylase 1, Transfection, Retinoblastoma Protein, Histone Deacetylases, Transcription (biology), Prohibitins, Tumor Cells, Cultured, Genetics, Humans, Nuclear Receptor Co-Repressor 1, E2F1, Prohibitin, E2F, Molecular Biology, Psychological repression, DNA Primers, Cell Nucleus, Base Sequence, biology, Nuclear Proteins, Proteins, Promoter, Cell cycle, Molecular biology, Gene Expression Regulation, Neoplastic, Repressor Proteins, Histone, Gene Expression Regulation, biology.protein, Female |
| الوصف: | The potential tumor suppressor protein prohibitin can prevent cell proliferation and this required its binding to the Rb protein. Prohibitin could repress the transcriptional activity of E2F family members and this required a part of the marked box region of E2F. The sub-cellular localization of prohibitin has been variously attributed to the mitochondria as well as the inner cell membrane. Here we show that a subset of prohibitin molecules are present in the nucleus where it co-localizes with the Rb protein. Deletion of a putative amino-terminal membrane-docking domain of prohibitin had no effect on its ability to suppress cell proliferation or inhibit E2F activity. Our experiments show that a 53 amino-acid stretch of E2F1 is sufficient for being targeted by prohibitin; fusion of this region to GAL4-VP16 construct could make it susceptible to prohibitin-mediated, but not Rb-mediated repression. Prohibitin, like Rb, could repress transcription from SV40 and major late promoters when recruited directly to DNA. Prohibitin mediated transcriptional repression required histone-deacetylase activity, but unlike Rb, additional co-repressors like N-CoR are also involved. Repression by prohibitin correlates with histone deacetylation on promoters and this was reversed by IgM stimulation of cells; IgM did not affect Rb-mediated repression or deacetylation of the promoters. Prohibitin thus appears to repress E2F-mediated transcription utilizing different molecular mediators and facilitate channeling of specific signaling pathways to the cell cycle machinery. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d051fc15aad6bbf95a3d5031e8782084Test https://doi.org/10.1038/sj.onc.1205944Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d051fc15aad6bbf95a3d5031e8782084 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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