Calpain cleavage regulates the protein stability of p73

Eliana Munarriz, Daniele Bano, A. Emre Sayan, Mario Rossi, Gerry Melino, Pierluigi Nicotera

Research output: Contribution to journalArticlepeer-review


The function of p73, a transcription factor belonging to the p53 family, is finely regulated by its steady-state protein stability. p73 protein degradation/stabilization can be regulated by mechanisms in part dependent on the ubiquitin proteasome system (UPS): (i) Itch/NEDD4-like UPS degradation, (ii) NEDD8 UPS degradation, and (iii) NQO1 20S proteasome-dependent (but ubiquitin-independent) breakdown. Here, we show that, in vitro, Calpain I can cleave p73 at two distinct sites: the first proline-rich region and within the oligomerization domain. Consequently, different p73 isoforms can be degraded by calpains, i.e., both N-terminal isoforms (TAp73 and ΔNp73) as well as the C-terminal isoforms (α, β, γ, δ). Moreover, overexpression of the specific endogenous calpain inhibitor, calpastatin, in cultured cells increased the steady-state p73 level. This suggests that calpains may play a physiological role in the regulation of p73 protein stability.

Original languageEnglish
Pages (from-to)954-960
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - Aug 5 2005


  • Apoptosis
  • Calcium
  • Calpains
  • Calpastatin
  • Cell death
  • Neural development
  • p53
  • p73
  • Protein degradation
  • Protein stability
  • TCR-apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology


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