Role of the calpain-calpastatin system in the density-dependent growth arrest

Roberto Stifanese, Monica Averna, Roberta De Tullio, Franca Salamino, Claudia Cantoni, Maria Cristina Mingari, Carola Prato, Sandro Pontremoli, Edon Melloni

Research output: Contribution to journalArticlepeer-review

Abstract

In dividing cells calpastatin diffuses from aggregates into cytosol, indicating the requirement for a tight regulation of calpain. Accordingly, the involvement of the calpain-calpastatin system in cell proliferation and in the density-dependent growth arrest was studied in JA3 cells stably transfected with a calpastatin form permanently localized in cytosol. In calpastatin overexpressing cells, cell cycle rate is 50% reduced, and cells enter the ungrowing, still fully reversible, stage at a 3-fold higher cell density. Furthermore, in cell density growth arrest phase, down regulation of α- and θ-PKC isoforms, as well as FAK and talin occurs. In calpastatin overexpressing cells, degradation of these calpain substrate proteins is prevented and delayed. Thus, calpain activity plays a crucial role in inducing the cell entry into a functional quiescent phase.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume479
Issue number2
DOIs
Publication statusPublished - Nov 15 2008

Keywords

  • Calpain
  • Calpastatin
  • Cell growth arrest
  • Cell proliferation
  • Down regulation
  • Focal adhesion kinase (FAK)
  • Protein kinase C
  • Talin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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