Retracted: In vivo potentiation of human oestrogen receptor α by Cdk7‐mediated phosphorylation

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 transactivation in vitro through Ser118 phosphorylation. To investigate an impact of Cdk7 on hERα transactivation in vivo, we assessed activity of hERα in a wild-type and cdk7 inactive mutant Drosophila that 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 in cdk7 inactive mutant Drosophila the wild-type hERα exhibited reduced response to the ligand; levels of transactivation by the hERα S118A mutant were not affected in these inactive cdk7 mutant flies. Furthermore, phosphorylation of hERα 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 hERαin vivo via Ser118 phosphorylation.