The adenoviral E1A protein relieves gene repression by receptors in v/vo displaces corepressors and unliganded thyroid hormone  

作　　者：Yukiyasu Sato Andrew Ding Rachel A Heimeier Ahmed F Yousef Joe S Mymryk Paul G Walfish Yun-Bo Shi 

机构地区：[1]Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, PCRM, NICHD, NIH, Bldg 18T, Rm 106, Bethesda, MD 20892, USA [2]Obstetrics Division, Department of Gynecology & Obstetrics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan [3]Departments of Oncology and Microbiology & Immunology, The University of Western Ontario, London, Ontario, Canada N6A 4L6 [4]Endocrine Division, Department of Medicine, Room 413, Mount Sinai Hospital 600 University Avenue, Toronto, Ontario, Canada M5G 1X5

出　　处：《Cell Research》2009年第6期783-792,共10页细胞研究（英文版）

摘　　要：The human adenovirus type 5 early region 1A （E1A） is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone （T3） receptors （TRs）. However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.

关 键 词：adenoviral E1A thyroid hormone receptor COREPRESSOR COACTIVATOR CHROMATIN 

分 类 号：Q572[生物学—生物化学] S839[农业科学—畜牧学]