This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meng, X. Articles by Walfish, P. G. Search for Related Content PubMed PubMed Citation Articles by Meng, X. Articles by Walfish, P. G.

Cellular Context of Coregulator and Adaptor Proteins Regulates Human Adenovirus 5 Early Region 1A-Dependent Gene Activation by the Thyroid Hormone Receptor

Samuel Lunenfeld Research Institute of Mount Sinai Hospital (X.M., Y.-F.Y., X.C., P.G.W.) and Department of Medicine (P.G.W.), Endocrine Division, University of Toronto Medical School, Toronto, Ontario, Canada M5G 1X5; Centre de Recherche Hotel-Dieu de Québec Université Laval (M.V.G.), Québec, Canada G1R 2J6; Departments of Oncology (J.S.M.), Physiology and Pharmacology (J.S.M.), and Microbiology and Immunology (M.S., J.S.M.), The University of Western Ontario and London Regional Cancer Centre, London, Ontario, Canada N6A 4L6; and Thyroid Unit (A.N.H.), Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Dr. Paul G. Walfish, Mount Sinai Hospital, Endocrine Unit, 600 University Avenue, Suite 781, Toronto, Ontario, Canada M5G 1X5. E-mail: walfish{at}mshri.on.ca.

In mammalian cells, the human adenovirus type 5 early region 1A (E1A) oncoprotein functions as a thyroid hormone (TH)-dependent activator of the thyroid hormone receptor (TR). Interestingly, in the cellular context of the yeast Saccharomyces cerevisiae, E1A acts as a TR-specific constitutive coactivator that is down-regulated by TH. TH reduces the interaction of E1A with the TR in yeast but not HeLa cells. The N-terminal 82 amino acids of E1A are sufficient for coactivation in yeast and residues 4–29 are essential. In yeast, expression of the nuclear receptor corepressor (N-CoR) could down-regulate constitutive transcriptional activation of the TR by E1A, whereas expression of the glucocorticoid receptor interacting protein 1 (GRIP-1) coactivator reconstituted the E1A-induced pattern of enhanced TH-dependent gene activation by TR observed in mammalian cells. We further show that the mating type switching gene (SWI)/sucrose nonfermenting (SNF) gene chromatin remodeling complex is required for both TH/GRIP-1- and E1A-dependent coactivator function, whereas the general control nonrepressed protein (GCN5)/alteration/deficiency in activation protein (ADA2) components of the SPT, ADA, GCN5, acetylation (SAGA) transcriptional adaptor complex are required for TH/GRIP-1, but not E1A-dependent activation of the TR. Taken together, these studies demonstrate that the novel TR-specific coactivator function of E1A in yeast depends on the SWI/SNF chromatin remodeling complex and can be further influenced by changes in the cellular complement of transcriptional coregulatory proteins.

NURSA Molecule Pages Link:

Nuclear Receptors:   TRα  |  TRβ  |  RXRγ

Coregulators:   TRIP1  |  GRIP1  |  NCOR

Ligands:   9-cis-Retinoic acid  |  Thyroid hormone

This article has been cited by other articles:

				P. Pelka, J. N. G. Ablack, G. J. Fonseca, A. F. Yousef, and J. S. Mymryk Intrinsic Structural Disorder in Adenovirus E1A: a Viral Molecular Hub Linking Multiple Diverse Processes J. Virol., August 1, 2008; 82(15): 7252 - 7263. [Full Text] [PDF]

				L. F. R. Velasco, M. Togashi, P. G. Walfish, R. P. Pessanha, F. N. Moura, G. B. Barra, P. Nguyen, R. Rebong, C. Yuan, L. A. Simeoni, et al. Thyroid Hormone Response Element Organization Dictates the Composition of Active Receptor J. Biol. Chem., April 27, 2007; 282(17): 12458 - 12466. [Abstract] [Full Text] [PDF]

				X. Meng, P. Webb, Y.-F. Yang, M. Shuen, A. F. Yousef, J. D. Baxter, J. S. Mymryk, and P. G. Walfish E1A and a nuclear receptor corepressor splice variant (N-CoRI) are thyroid hormone receptor coactivators that bind in the corepressor mode PNAS, May 3, 2005; 102(18): 6267 - 6272. [Abstract] [Full Text] [PDF]

				M. Rasti, R. J. A. Grand, J. S. Mymryk, P. H. Gallimore, and A. S. Turnell Recruitment of CBP/p300, TATA-Binding Protein, and S8 to Distinct Regions at the N Terminus of Adenovirus E1A J. Virol., May 1, 2005; 79(9): 5594 - 5605. [Abstract] [Full Text] [PDF]