title: CAC1 negatively regulates RARα activity through cooperation with HDAC.
abstract: Retinoic acid (RA) plays pleiotropic roles in cellular differentiation and animal development. RA responses are mediated by transcriptional activation by the retinoic acid receptor (RAR) and retinoid X receptor (RXR) in cooperation with various types of coregulators at RA-responsive gene promoters. Here, we identified CDK2-associated cullin (CAC1) as a novel type of RARα coregulator that interacts with RARα and inhibits its transcriptional activity. The CoRNR box of CAC1 is required for the binding to and inactivation of RARα. In addition, CAC1 cooperates with histone deacetylases (HDACs) to suppress RARα, probably by associating with HDAC. Finally, depletion of CAC1 increases RA-induced neuronal differentiation of P19 cells, a response accompanied by significant upregulation of the neuronal marker nestin. From these results, we suggest that CAC1 is a novel corepressor of RARα that cooperates with HDACs and is involved in the regulation of RA-induced cellular differentiation.
authors.affiliation: Department of Molecular Biology, BK21 Graduate Program, Dankook University, Yongin-si, Gyeonggi-do 448-701, Republic of Korea.
authors.forename: MinO
authors.initials: M
authors.lastname: Moon
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Um
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D034622:RNA Interference; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C546534:CACUL1 protein, human; D044842:Cullin Proteins; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D006655:Histone Deacetylases