title: Modulatory role of the anti-apoptotic protein kinase CK2 in the sub-cellular localization of Fas associated death domain protein (FADD).
abstract: The Fas associated death domain protein (FADD) is the key adaptor molecule of the apoptotic signal triggered by death receptors of the TNF-R1 superfamily. Besides its crucial role in the apoptotic machinery, FADD has proved to be important in many biological processes like tumorigenesis, embryonic development or cell cycle progression. In a process to decipher the regulatory mechanisms underlying FADD regulation, we identified the anti-apoptotic kinase, CK2, as a new partner and regulator of FADD sub-cellular localization. The blockade of CK2 activity induced FADD re-localization within the cell. Moreover, cytoplasmic FADD was increased when CK2β was knocked down. In vitro kinase and pull down assays confirmed that FADD could be phosphorylated by the CK2 holoenzyme. We found that phosphorylation is weak with CK2α alone and optimal in the presence of stoichiometric amounts of CK2α catalytic and CK2β regulatory subunit, showing that FADD phosphorylation is undertaken by the CK2 holoenzyme in a CK2β-driven fashion. We found that CK2 can phosphorylate FADD on the serine 200 and that this phosphorylation is important for nuclear localization of FADD. Altogether, our results show for the first time that multifaceted kinase, CK2, phosphorylates FADD and is involved in its sub-cellular localization. This work uncovered an important role of CK2 in stable FADD nuclear localization.
authors.affiliation: Inserm U1173, Université Versailles-Saint-Quentin, Saint-Quentin-En-Yvelines, France; Inserm U1016, CNRS, UMR 8104, Institut Cochin, Université Paris Descartes, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilmont
authors.affiliation: Inserm U1036, Biologie du Cancer et de l'Infection, CEA, Grenoble, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Filhol
authors.affiliation: CEA, DSV, Laboratoire d'Etude de la Dynamique des Protéomes, Grenoble, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Hesse
authors.affiliation: CEA, DSV, Laboratoire d'Etude de la Dynamique des Protéomes, Grenoble, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Couté
authors.affiliation: Inserm U1173, Université Versailles-Saint-Quentin, Saint-Quentin-En-Yvelines, France; UFR des Sciences de la Santé, Simone Veil, 78180 Montigny-Le-Bretonneux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hue
authors.affiliation: Inserm U1016, CNRS, UMR 8104, Institut Cochin, Université Paris Descartes, Paris, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Rémy-Tourneur
authors.affiliation: Inserm U1016, CNRS, UMR 8104, Institut Cochin, Université Paris Descartes, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mistou
authors.affiliation: Inserm U1036, Biologie du Cancer et de l'Infection, CEA, Grenoble, France. Electronic address: claude.cochet@cea.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Cochet
authors.affiliation: Inserm U1173, Université Versailles-Saint-Quentin, Saint-Quentin-En-Yvelines, France; UFR des Sciences de la Santé, Simone Veil, 78180 Montigny-Le-Bretonneux, France. Electronic address: gilles.chiocchia@inserm.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Chiocchia
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000502:physiology
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D047390:Casein Kinase II
keywords: CK2; FADD; Nuclear localization; Phosphorylation; Regulation