The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2001-03-30Keywords
Amino Acid SequenceCell Line
Cloning, Molecular
DNA Repair
Fungal Proteins
Humans
Molecular Sequence Data
*Proteins
Receptors, Estrogen
Receptors, Interferon
*Saccharomyces cerevisiae Proteins
Sequence Homology, Amino Acid
*TATA-Binding Protein Associated Factors
Trans-Activation (Genetics)
Trans-Activators
*Transcription Factor TFIID
Transcription Factor TFIIH
Transcription Factors
*Transcription Factors, TFII
Tumor Cells, Cultured
Two-Hybrid System Techniques
Yeasts
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Steroid/nuclear hormone receptors are ligand-dependent transcriptional regulators that control gene expression in a wide array of biological processes. The transcriptional activity of the receptors is mediated by an N-terminal ligand-independent transcriptional activation function AF-1 and a C-terminal ligand-dependent transcriptional activation function AF-2. The nuclear receptor coactivator RAC3 (also known as AIB1/ACTR/pCIP/TRAM-1/SRC-3) is amplified in breast cancer cells, where it forms a complex with estrogen receptor (ER) and enhances AF-2 activity of the receptor. Here, we identify a putative human homologue of the yeast DNA repair and transcriptional regulator MMS19 as a RAC3-interacting protein. The human MMS19 interacts with the N-terminal PAS-A/B domain of RAC3 in vivo and in vitro through a conserved C-terminal domain. Interestingly, the human MMS19 also interacts with estrogen receptors in a ligand-independent manner but not with retinoic acid receptor or thyroid hormone receptor. Overexpression of the interacting domain of hMMS19 strongly inhibits ER-mediated transcriptional activation, indicating a dominant negative activity. In contrast, over expression of the full-length hMMS19 enhances ER-mediated transcriptional activation. We find that hMMS19 stimulates the AF-1 activity of ERalpha, but not the AF-2 activity, suggesting that hMMS19 may be an AF-1-specific transcriptional coactivator of estrogen receptor.Source
J Biol Chem. 2001 Jun 29;276(26):23962-8. Epub 2001 Mar 28. Link to article on publisher's siteDOI
10.1074/jbc.M101041200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42390PubMed ID
11279242Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M101041200
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