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Calpain cleavage regulates the protein stability of p73

Eliana Munarriz1, Daniele Bano, A Emre Sayan

  • 1Medical Research Council, Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK.

Biochemical and Biophysical Research Communications
|June 25, 2005
PubMed

Insights

Calpains, a type of protease, can degrade the p73 protein, a member of the p53 family. Inhibiting calpains increases p73 protein levels, suggesting calpains regulate p73 stability.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The stability of p73 protein, a transcription factor in the p53 family, is crucial for its function.
  • p73 protein degradation is partly regulated by the ubiquitin proteasome system (UPS), involving mechanisms like Itch/NEDD4-like degradation, NEDD8 UPS degradation, and NQO1 20S proteasome breakdown.

Purpose of the Study:

  • To investigate the role of calpains in the regulation of p73 protein stability.
  • To identify the specific sites of p73 cleavage by calpains and the impact on different p73 isoforms.

Main Methods:

  • In vitro cleavage assays using purified Calpain I and p73.
  • Overexpression of calpastatin, a calpain inhibitor, in cultured cells.
  • Analysis of p73 protein levels and stability.

Main Results:

  • Calpain I was shown to cleave p73 at two distinct sites: the proline-rich region and the oligomerization domain.
  • Both N-terminal (TAp73, DeltaNp73) and C-terminal (alpha, beta, gamma, delta) p73 isoforms are susceptible to calpain-mediated degradation.
  • Overexpression of calpastatin led to an increase in steady-state p73 levels in cultured cells.

Conclusions:

  • Calpains can directly degrade p73 protein, affecting various isoforms.
  • Calpains play a significant physiological role in regulating p73 protein stability.
  • Understanding calpain-p73 interaction provides insights into p53 family protein regulation.

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