Abstract
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 language | English |
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Pages (from-to) | 954-960 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 333 |
Issue number | 3 |
DOIs | |
Publication status | Published - Aug 5 2005 |
Keywords
- Apoptosis
- Calcium
- Calpains
- Calpastatin
- Cell death
- Neural development
- p53
- p73
- Protein degradation
- Protein stability
- TCR-apoptosis
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology