Trim24 (Tif1 alpha): an essential 'brake' for retinoic acid-induced transcription to prevent liver cancer
| Autor: | Régine Losson, Benjamin Herquel, Johan Tisserand, Marius Teletin, Khalid Ouararhni, Konstantin Khetchoumian |
|---|---|
| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Peney, Maité, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Aging
Cell type Transcription Genetic Receptors Retinoic Acid Retinoic acid Tretinoin Biology TRIM24 Polyploidy Mice chemistry.chemical_compound Transcription (biology) Gene expression Animals Homeostasis Receptor Molecular Biology Transcription factor Cell Proliferation [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] Retinoic Acid Receptor alpha Liver Neoplasms Nuclear Proteins Cell Biology [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] Cell biology Phenotype Biochemistry Nuclear receptor chemistry Hepatocytes Transcription Factors Developmental Biology |
| Zdroj: | Cell Cycle Cell Cycle, Taylor & Francis, 2008, 7 (23), pp.3647-52 ResearcherID Cell Cycle, 2008, 7 (23), pp.3647-52 |
| ISSN: | 1538-4101 1551-4005 |
| Popis: | International audience; Retinoic acid (RA), the active derivative of vitamin A, is an important signaling molecule that controls various developmental processes and influence the proliferation and differentiation of a variety of cell types. RA exerts its biological functions primarily through binding to and activating nuclear RA receptors (RARs, which include the RAR alpha, beta and gamma isotypes RARA, RARB and RARC). Aberrant expression or impaired function of these nuclear receptors has been linked to diverse types of cancer. RARs are RA-dependent transcription factors that regulate gene expression through the recruitment of different co-regulators (co-activators and co-repressors). TRIM24 (formerly known as TIF1 alpha) was among the first co-regulators identified as interacting with RARs in a ligand-dependent fashion, and it was recently shown to function in mice as a potent liver-specific tumor suppressor by attenuating Rara-mediated transcription. The fact that Trim24(-/-), but not Trim24(-/-)Rara(+/-), mutant mice are highly predisposed to the development of hepatocellular carcinoma (HCC) has significant implications in cancer research. This result, along with the observation that in response to pharmacological inhibition of the RA signaling, hepatocytes lacking Trim24 loose their ability to proliferate, strongly implicates Rara as a proto-oncogene in hepatocytes and demonstrates that overactivated RA signaling is deleterious to liver homeostasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|