RGD Reference Report - Identification and characterization of a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors. - Rat Genome Database

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Identification and characterization of a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors.

Authors: Ko, L  Cardona, GR  Henrion-Caude, A  Chin, WW 
Citation: Ko L, etal., Mol Cell Biol 2002 Jan;22(1):357-69.
RGD ID: 628392
Pubmed: PMID:11739747   (View Abstract at PubMed)
PMCID: PMC134202   (View Article at PubMed Central)

Gene activation mediated by nuclear receptors is regulated in a tissue-specific manner and requires interactions between nuclear receptors and their cofactors. Here, we identified and characterized a tissue-specific coactivator, GT198, that interacts with the DNA-binding domains of nuclear receptors. GT198 was originally described as a genomic transcript that mapped to the human breast cancer susceptibility locus 17q12-q21 with unknown function. We show that GT198 exhibits a tissue-specific expression pattern in which its mRNA is elevated in testis, spleen, thymus, pituitary cells, and several cancer cell lines. GT198 is a 217-amino-acid nuclear protein that contains a leucine zipper required for its dimerization. In vitro binding and yeast two-hybrid assays indicated that GT198 interacted with nuclear receptors through their DNA-binding domains. GT198 potently stimulated transcription mediated by estrogen receptor alpha and beta, thyroid hormone receptor beta1, androgen receptor, glucocorticoid receptor, and progesterone receptor. However, the action of GT198 was distinguishable from that of the ligand-binding domain-interacting nuclear receptor coactivators, such as TRBP, CBP, and SRC-1, with respect to basal activation and hormone sensitivity. Furthermore, protein kinase A, protein kinase C, and mitogen-activated protein kinase can phosphorylate GT198 in vitro, and cotransfection of these kinases regulated the transcriptional activity of GT198. These data suggest that GT198 is a tissue-specific, kinase-regulated nuclear receptor coactivator that interacts with the DNA-binding domains of nuclear receptors.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of transcription by RNA polymerase II  IDA 628392 RGD 
protein-containing complex assembly  TAS 628392dimerizationRGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Psmc3ip  (PSMC3 interacting protein)

Objects referenced in this article
Gene Mapk1 mitogen activated protein kinase 1 Rattus norvegicus
Gene Rxra retinoid X receptor alpha Rattus norvegicus

Additional Information