Procaspase-2S inhibits procaspase-3 processing and activation, preventing ROCK-1-mediated apoptotic blebbing and body formation in human B lymphoma Namalwa cells.
Procaspase-2S has been reported to selectively prevent membrane blebbing and apoptotic body formation in human monocytic-like leukemic U937 cells after etoposide (VP-16) treatment (Droin et al., Oncogene 20. 260-269, 2001). Here, we show that procaspase-2S overexpressed in human B lymphoma Namalwa cells inhibits procaspase-3 processing and activation, preventing cleavage and activation of Rho GTPase-associated ROCK-1 kinase. Failure of ROCK-1 activation in Namalwa cells correlates with a sustained delay in the appearance of membrane blebbing and apoptotic body formation after VP-16 treatment. Reciprocal coimmunoprecipitation experiments indicate that procaspase-2S binds to procaspase-3, but not procaspase-2L and -9 in untreated and VP-16-treated Namalwa cells. These data suggest that procaspase-2S-mediated anti-apoptotic effects are associated with inhibition of the processing and activation of procaspase-3 in VP-16-treated cells.
Parent
N
N
Centre de Recherche, Centre Hospitalier de l'Université of Montréal, Hôpital Notre-Dame and Institut du Cancer de Montréal, Quebec, Canada.
Sané
A-T
AT
Droin
N
N
Bertrand
R
R
D017209:Apoptosis; D015153:Blotting, Western; D053143:Caspase 2; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D009000:Monocytes / Q000166:cytology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors; D014162:Transfection; D020298:U937 Cells; D054460:rho-Associated Kinases
D061945:Caspase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D005047:Etoposide; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C505407:CASP3 protein, human; D053143:Caspase 2; D053148:Caspase 3; D020169:Caspases