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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

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

Franck Vandermoere1, Ikram El Yazidi-Belkoura, Christian Slomianny

  • 1ERI-8 INSERM, Growth factor signaling in breast cancer. Functional proteomics, University of Sciences and Technologies Lille, 59655 Villeneuve d'Ascq, France.

The Journal of Biological Chemistry
|March 23, 2006
PubMed

Insights

The serine/threonine kinase Akt targets the valosin-containing protein (VCP), a key player in cell survival. This study identifies VCP phosphorylation by Akt, revealing its role in cell growth and apoptosis signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The serine/threonine kinase Akt is crucial for cell survival and growth.
  • The precise mechanisms and signaling partners of Akt are not fully understood.

Purpose of the Study:

  • To identify novel Akt signaling partners using a proteomics approach.
  • To elucidate the role of the valosin-containing protein (VCP) in Akt signaling pathways.

Main Methods:

  • Proteomics analysis of Akt-interacting proteins in MCF-7 breast cancer cells.
  • Mass spectrometry to identify co-immunoprecipitated proteins.
  • Site-directed mutagenesis to pinpoint Akt phosphorylation sites on VCP.
  • Confocal microscopy for Akt and VCP co-localization studies.
  • Small interfering RNA (siRNA) to assess VCP's functional role.

Main Results:

  • Valosin-containing protein (VCP) was identified as an Akt signaling target.
  • VCP undergoes Akt-mediated phosphorylation at Ser-351, Ser-745, and Ser-747 upon growth factor stimulation.
  • Akt and VCP co-localize within cells following Akt activation.
  • VCP depletion via siRNA inhibited growth factor-induced NF-kappaB activation and promoted apoptosis.

Conclusions:

  • VCP is a direct and essential target of Akt signaling.
  • Akt-mediated phosphorylation of VCP plays a significant role in regulating cell growth, survival, and apoptosis.
  • These findings reveal a novel regulatory axis in cellular signaling pathways.

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