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¹ The Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan
² SORST, Japan Science and Technology, Kawaguchi, Saitama, Japan

Phosphorylation of the Ser¹¹⁸ residue in the N-terminal A/B domain of the human oestrogen receptor  (hER) by mitogen-activated protein kinase (MAPK), stimulated via growth factor signalling pathways, is known to potentiate ER ligand-induced transactivation function. Besides MAPK, cyclin dependent kinase 7 (Cdk7) in the TFIIH complex has also been found to potentiate hER transactivation in vitro through Ser¹¹⁸ phosphorylation. To investigate an impact of Cdk7 on hER transactivation in vivo, we assessed activity of hER in a wild-type and cdk7 inactive mutant Drosophila that ectopically expressed hER 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 hER expressed in the fly tissues was transcriptionally functional and adequately responded to hER ligands in the patterns similar to those observed in mammalian cells. Replacement of Ser¹¹⁸ with alanine in hER (S118A mutant) significantly reduced the ligand-induced hER transactivation function. Importantly, while in cdk7 inactive mutant Drosophila the wild-type hER exhibited reduced response to the ligand; levels of transactivation by the hER S118A mutant were not affected in these inactive cdk7 mutant flies. Furthermore, phosphorylation of hER at Ser¹¹⁸ has been observed in vitro by both human and Drosophila Cdk7. Our findings demonstrate that Cdk7 is involved in regulation of the ligand-induced transactivation function of hER in vivo via Ser¹¹⁸ phosphorylation.

^* Correspondence: Email: uskato{at}mail.ecc.u-tokyo.ac.jp

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