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http://purl.uniprot.org/citations/10428798http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10428798http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10428798http://www.w3.org/2000/01/rdf-schema#comment"Both estradiol binding and phosphorylation regulate transcriptional activation by the human estrogen receptor alpha (ER). We have previously shown that activation of the cyclin A-CDK2 complex by overexpression of cyclin A leads to enhanced ER-dependent transcriptional activation and that the cyclin A-CDK2 complex phosphorylates the ER N-terminal activation function-1 (AF-1) between residues 82 and 121. Within ER AF-1, serines 104, 106, and 118 represent potential CDK phosphorylation sites, and in this current study, we ascertain their importance in mediating cyclin A-CDK2-dependent enhancement of ER transcriptional activity. Cyclin A overexpression does not enhance transcriptional activation by an ER derivative bearing serine-to-alanine changes at residues 104, 106, and 118. Likewise, the cyclin A-CDK2 complex does not phosphorylate this triple-mutated derivative in vitro. Individual serine-to-alanine mutations at residues 104 and 106, but not 118, decrease ER-dependent transcriptional enhancement in response to cyclin A. The same relationship holds for ER phosphorylation by cyclin A-CDK2 in vitro. Finally, enhancement of ER transcriptional activation by cyclin A is evident in the absence and presence of estradiol, as well as in the presence of tamoxifen, suggesting that the effect of the cyclin A-CDK2 on ER transcriptional activation is AF-2-independent. These results indicate that the enhancement of ER transcriptional activation by the cyclin A-CDK2 complex is mediated via the AF-1 domain by phosphorylation of serines 104 and 106. We propose that these residues control ER AF-1 activity in response to signals that affect cyclin A-CDK2 function."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.org/dc/terms/identifier"doi:10.1074/jbc.274.32.22296"xsd:string
http://purl.uniprot.org/citations/10428798http://purl.org/dc/terms/identifier"doi:10.1074/jbc.274.32.22296"xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/author"Garabedian M.J."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/author"Garabedian M.J."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/author"Rogatsky I."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/author"Rogatsky I."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/author"Trowbridge J.M."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/author"Trowbridge J.M."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/pages"22296-22302"xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/pages"22296-22302"xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/title"Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/title"Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex."xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/volume"274"xsd:string
http://purl.uniprot.org/citations/10428798http://purl.uniprot.org/core/volume"274"xsd:string
http://purl.uniprot.org/citations/10428798http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10428798
http://purl.uniprot.org/citations/10428798http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10428798
http://purl.uniprot.org/citations/10428798http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10428798
http://purl.uniprot.org/citations/10428798http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10428798