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Article Dans Une Revue Journal of Biological Chemistry Année : 2006

The Valosin-containing Protein (VCP) Is a Target of Akt Signaling Required for Cell Survival

Ikram El Yazidi-Belkoura
  • Fonction : Auteur
Christian Slomianny
  • Fonction : Auteur
Yohann Demont
  • Fonction : Auteur
  • PersonId : 1151783
  • IdRef : 125012322
Gabriel Bidaux
Eric Adriaenssens
  • Fonction : Auteur
Jérôme Lemoine
  • Fonction : Auteur
Hubert Hondermarck
  • Fonction : Auteur

Résumé

The serine/threonine kinase Akt is a key mediator of cell survival and growth, but its precise mechanism of action, and more specifically, the nature of its signaling partners largely remain to be elucidated. We show, using a proteomics-based approach, that the valosin-containing protein (VCP), a member of the AAA (ATPases associated with a variety of cellular activities) family, is a target of Akt signaling. SDS-PAGE of Akt co-immunoprecipitated proteins obtained from MCF-7 breast cancer cells revealed the increase of a 97-kDa band under Akt activation. Mass spectrometry analysis allowed the identification of VCP, and we have shown a serine/threonine phosphorylation on an Akt consensus site upon activation by growth factors. Site-directed mutagenesis identified Ser-351, Ser-745, and Ser-747 as Akt phosphorylation sites on VCP. Confocal microscopy indicated a co-localization between Akt and VCP upon Akt stimulation. Interestingly, small interfering RNA against VCP induced an inhibition of the growth factor-induced activation of NF-B and a potent pro-apoptotic effect. Together, these data identify VCP as an essential target of Akt signaling.
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Dates et versions

hal-03030155 , version 1 (29-11-2020)

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Franck Vandermoere, Ikram El Yazidi-Belkoura, Christian Slomianny, Yohann Demont, Gabriel Bidaux, et al.. The Valosin-containing Protein (VCP) Is a Target of Akt Signaling Required for Cell Survival. Journal of Biological Chemistry, 2006, 281 (20), pp.14307 - 14313. ⟨10.1074/jbc.m510003200⟩. ⟨hal-03030155⟩
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