Open AccessRegulation of estrogen receptor transcriptional enhancement by the cyclin A/Cdk2 complex
Author(s) -
Janet M. Trowbridge,
Inez Rogatsky,
Michael J. Garabedian
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.19.10132
Subject(s) - cyclin dependent kinase , cyclin a2 , cyclin a , cyclin e , cyclin d , cyclin dependent kinase 2 , ectopic expression , cyclin b , estrogen receptor , cyclin , cancer research , biology , microbiology and biotechnology , cyclin dependent kinase complex , hela , chemistry , cell cycle , kinase , cell culture , biochemistry , protein kinase a , cell , cancer , genetics , breast cancer
We have found that ectopic expression of cyclin A increases hormone-dependent and hormone-independent transcriptional activation by the estrogen receptorin vivo in a number of cell lines, including HeLa cells, U-2 OS osteosarcoma cells and Hs 578Bst breast epithelial cells. This effect can be further enhanced in HeLa cells by the concurrent expression of the cyclin-dependent kinase activator, cyclin H, and cdk7, and abolished by expression of the cdk inhibitor, p27KIP1 , or by the expression of a dominant negative catalytically inactive cdk2 mutant. ER is phosphorylated between amino acids 82 and 121in vitro by the cyclin A/cdk2 complex and incorporation of phosphate into ER is stimulated by ectopic expression of cyclin Ain vivo . Together, these results strongly suggest a direct role for the cyclin A/cdk2 complex in phosphorylating ER and regulating its transcriptional activity.