Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 479, Issue 2, Pages 145-152Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2008.09.002
Keywords
Cell proliferation; Cell growth arrest; Calpain; Calpastatin; Down regulation; Protein kinase C; Focal adhesion kinase (FAK); Talin
Categories
Funding
- Italian Ministry of University
- University of Genoa, Italy
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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 Fate 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 alpha- and theta-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. (C) 2008 Elsevier Inc. All rights reserved.
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