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Ito, S., Takeyama, K., Yamamoto, A., Sawatsubashi, S., Shirode, Y., Kouzmenko, A., Tabata, T., Kato, S. (2004). In vivo potentiation of human oestrogen receptor α by Cdk7-mediated phosphorylation.  Genes Cells 9(10): 983--992.
FlyBase ID
FBrf0185578
Publication Type
Research paper
Abstract

Phosphorylation of the Ser(118) residue in the N-terminal A/B domain of the human oestrogen receptor alpha (hERalpha) by mitogen-activated protein kinase (MAPK), stimulated via growth factor signalling pathways, is known to potentiate ERalpha ligand-induced transactivation function. Besides MAPK, cyclin dependent kinase 7 (Cdk7) in the TFIIH complex has also been found to potentiate hERalpha transactivation in vitro through Ser(118) phosphorylation. To investigate an impact of Cdk7 on hERalpha transactivation in vivo, we assessed activity of hERalpha in a wild-type and cdk7 inactive mutant Drosophila that ectopically expressed hERalpha 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 hERalpha expressed in the fly tissues was transcriptionally functional and adequately responded to hERalpha ligands in the patterns similar to those observed in mammalian cells. Replacement of Ser(118) with alanine in hERalpha (S118A mutant) significantly reduced the ligand-induced hERalpha transactivation function. Importantly, while in cdk7 inactive mutant Drosophila the wild-type hERalpha exhibited reduced response to the ligand; levels of transactivation by the hERalpha S118A mutant were not affected in these inactive cdk7 mutant flies. Furthermore, phosphorylation of hERalpha at Ser(118) 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 hERalphain vivo via Ser(118) phosphorylation.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genes Cells
    Title
    Genes to cells : devoted to molecular & cellular mechanisms
    Publication Year
    1996-
    ISBN/ISSN
    1356-9597
    Data From Reference
    Aberrations (1)
    Alleles (10)
    Genes (7)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (8)