Cellular context of coregulator and adaptor proteins regulates human adenovirus 5 early region 1A-dependent gene activation by the thyroid hormone receptor.
Mol Endocrinol
; 17(6): 1095-105, 2003 Jun.
Article
in En
| MEDLINE
| ID: mdl-12637585
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Saccharomyces cerevisiae
/
Transcription Factors
/
Receptors, Thyroid Hormone
/
Nuclear Proteins
/
Chromosomal Proteins, Non-Histone
/
Gene Expression Regulation
/
Adenovirus E1A Proteins
Limits:
Humans
Language:
En
Journal:
Mol Endocrinol
Journal subject:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Year:
2003
Document type:
Article