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- Title
In vivopotentiation of human oestrogen receptor α by Cdk7-mediated phosphorylation.
- Authors
Ito, Saya; Takeyama, Ken-ichi; Yamamoto, Ayako; Sawatsubashi, Shun; Shirode, Yuko; Kouzmenko, Alexander; Tabata, Tetsuya; Kato, Shigeaki
- Abstract
Phosphorylation of the Ser118 residue in the N-terminal A/B domain of the human oestrogen receptor α (hERα) by mitogen-activated protein kinase (MAPK), stimulated via growth factor signalling pathways, is known to potentiate ERα ligand-induced transactivation function. Besides MAPK, cyclin dependent kinase 7 (Cdk7) in the TFIIH complex has also been found to potentiate hERα transactivationin vitrothrough Ser118 phosphorylation. To investigate an impact of Cdk7 on hERα transactivationin vivo, we assessed activity of hERα in a wild-type andcdk7inactive mutantDrosophilathat ectopically expressed hERα in the eye disc. Ectopic expression of the wild-type or mutant receptors, together with a green fluorescent protein (GFP) reporter gene, allowed us to demonstrate that hERα expressed in the fly tissues was transcriptionally functional and adequately responded to hERα ligands in the patterns similar to those observed in mammalian cells. Replacement of Ser118 with alanine in hERα (S118A mutant) significantly reduced the ligand-induced hERα transactivation function. Importantly, while incdk7inactive mutantDrosophilathe wild-type hERα exhibited reduced response to the ligand; levels of transactivation by the hERα S118A mutant were not affected in these inactivecdk7mutant flies. Furthermore, phosphorylation of hERα at Ser118 has been observedin vitroby both human andDrosophilaCdk7. Our findings demonstrate that Cdk7 is involved in regulation of the ligand-induced transactivation function of hERα in vivovia Ser118 phosphorylation.
- Subjects
PHOSPHORYLATION; CELLULAR control mechanisms; PROTEIN kinases; CYTOKINES; GROWTH factors; STEROID hormones
- Publication
Genes to Cells, 2004, Vol 9, Issue 10, p983
- ISSN
1356-9597
- Publication type
Article
- DOI
10.1111/j.1365-2443.2004.00777.x