title: ATF7 is stabilized during mitosis in a CDK1-dependent manner and contributes to cyclin D1 expression.
abstract: The transcription factor ATF7 undergoes multiple post-translational modifications, each of which has distinct effects upon ATF7 function. Here, we show that ATF7 phosphorylation on residue Thr112 exclusively occurs during mitosis, and that ATF7 is excluded from the condensed chromatin. Both processes are CDK1/cyclin B dependent. Using a transduced neutralizing monoclonal antibody directed against the Thr112 epitope in living cells, we could demonstrate that Thr112 phosphorylation protects endogenous ATF7 protein from degradation, while it has no effect on the displacement of ATF7 from the condensed chromatin. The crucial role of Thr112 phosphorylation in stabilizing ATF7 protein during mitosis was confirmed using phospho-mimetic and phospho-deficient mutants. Finally, silencing ATF7 by CRISPR/Cas9 technology leads to a decrease of cyclin D1 protein expression levels. We propose that mitotic stabilized ATF7 protein re-localizes onto chromatin at the end of telophase and contributes to induce the cyclin D1 gene expression.
authors.affiliation: a Université de Strasbourg; UMR7242 Biotechnologie et Signalisation Cellulaire; Ecole Supérieure de Biotechnologie de Strasbourg ; Illkirch Cedex , France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Schaeffer
authors.forename: Marc
authors.initials: M
authors.lastname: Vigneron
authors.forename: Annie-Paule
authors.initials: AP
authors.lastname: Sibler
authors.forename: Mustapha
authors.initials: M
authors.lastname: Oulad-Abdelghani
authors.forename: Bruno
authors.initials: B
authors.lastname: Chatton
authors.forename: Mariel
authors.initials: M
authors.lastname: Donzeau
mesh_terms: D051696:Activating Transcription Factors / Q000378:metabolism*; D000818:Animals; D016203:CDC2 Protein Kinase; D002843:Chromatin / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D015533:Transcriptional Activation
chemical_list: C427752:ATF7 protein, human; D051696:Activating Transcription Factors; C530104:CCND1 protein, human; D002843:Chromatin; D019938:Cyclin D1; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: ATF7; cell-cycle; cyclin D1; intrabody; mitosis; phosphorylation