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The valosin-containing protein (VCP) is a target of Akt signaling required for cell survival.

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-kappaB and a potent pro-apoptotic effect. Together, these data identify VCP as an essential target of Akt signaling.

Pubmed ID: 16551632

Authors

  • Vandermoere F
  • El Yazidi-Belkoura I
  • Slomianny C
  • Demont Y
  • Bidaux G
  • Adriaenssens E
  • Lemoine J
  • Hondermarck H

Journal

The Journal of biological chemistry

Publication Data

May 19, 2006

Associated Grants

None

Mesh Terms

  • Adenosine Triphosphatases
  • Apoptosis
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Survival
  • Humans
  • Mass Spectrometry
  • Mutagenesis, Site-Directed
  • NF-kappa B
  • Phosphorylation
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-akt
  • RNA, Small Interfering
  • Serine
  • Signal Transduction