title: Phosphorylation of an N-terminal motif enhances DNA-binding activity of the human SRY protein.
abstract: Of the several strategies that eukaryotes have evolved to modulate transcription factor activity, phosphorylation is regarded as one of the major mechanisms in signal-dependent transcriptional control. To conclusively demonstrate that the human sex-determining gene SRY is affected by such a post-translational control mechanism, we have analyzed its phosphorylation status in living cells. In the present study, we show that the cyclic AMP-dependent protein kinase (PKA) phosphorylates the human SRY protein in vitro as well as in vivo on serine residues located in the N-terminal part of the protein. This phosphorylation event was shown to positively regulate SRY DNA-binding activity and to enhance the ability of SRY to inhibit a basal promoter activity located downstream of an SRY DNA-binding site concatamer. Together these results strongly support the hypothesis that human SRY is a natural substrate for PKA in vivo and that this phosphorylation significantly modulates its major activity, DNA-binding, thereby possibly altering its biological function.
authors.affiliation: Centre de Recherche de Biochimie Macromoléculaire, ERS155 CNRS, 1919 route de Mende, BP 5051, 34033 Montpellier Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Desclozeaux
authors.forename: F
authors.initials: F
authors.lastname: Poulat
authors.forename: P
authors.initials: P
authors.lastname: de Santa Barbara
authors.forename: J P
authors.initials: JP
authors.lastname: Capony
authors.forename: P
authors.initials: P
authors.lastname: Turowski
authors.forename: P
authors.initials: P
authors.lastname: Jay
authors.forename: C
authors.initials: C
authors.lastname: Méjean
authors.forename: B
authors.initials: B
authors.lastname: Moniot
authors.forename: B
authors.initials: B
authors.lastname: Boizet
authors.forename: P
authors.initials: P
authors.lastname: Berta
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D004247:DNA