Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3

Paroni, G Henderson, C Schneider, C Brancolini, C

G. Paroni et al., Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3, J BIOL CHEM, 276(24), 2001, pp. 21907-21915

48

INGLESE

Article

Biochemistry & Biophysics

JOURNAL OF BIOLOGICAL CHEMISTRY

0021-9258 → ACNP

276

24

2001

21907 - 21915

ISI

0021-9258(20010615)276:24<21907:CAIDOC>2.0.ZU;2-5

Mammalian caspases are a family of cysteine proteases that plays a critical role in apoptosis, We have analyzed caspase-2 processing in human cell lin es containing defined mutations in caspase-3 and caspase-9, Here we demonst rate that caspase-2 processing, during cell death induced by UV irradiation , depends both on caspase-9 and caspase-3 activity, while, during TNF-alpha -dependent apoptosis, capase-2 processing is independent of caspase-9 but still requires caspase-3, In vitro procaspase-2 is the preferred caspase cl eaved by caspase-3, while caspase-7 cleaves procaspase-2 with reduced effic iency. We have also demonstrated that caspase-2-mediated apoptosis requires caspase-9 and that cells co-expressing caspase-2 and a dominant negative f orm of caspase-9 are impaired in activating a normal apoptotic response and release cytochrome c into the cytoplasm, Our findings suggest a role playe d by caspase-2 as a regulator of the mitochondrial integrity and open quest ions on the mechanisms responsible for its activation during cell death.