Cleavage of zetaPKC but not lambda/iotaPKC by caspase-3 during UV-induced apoptosis.
The stimulation of caspases is a critical event in apoptotic cell death. Several kinases critically involved in cell proliferation pathways have been shown to be cleaved by caspase-mediated mechanisms. Thus, the degradation of delta protein kinase C (PKC) and MEKK-1 by caspase-3 generates activated fragments corresponding to their catalytic domains, consistent with the observations that both enzymes are important for apoptosis. In contrast, other kinases reported to have anti-apoptotic properties, such as Raf-1 and Akt, are inactivated by proteolytic degradation by the caspase system. Since the atypical PKCs have been shown to play critical roles in cell survival, in the study reported here we have addressed the potential degradation of these PKCs by the caspase system in UV-irradiated HeLa cells. Herein we show that although zetaPKC and lambda/iotaPKC are both inhibited in UV-treated cells, only zetaPKC but not lambda/iotaPKC is cleaved by a caspase-mediated process. This cleavage generates a fragment that corresponds to its catalytic domain that is enzymatically inactive. The sequence where caspase-3 cleaves zetaPKC was mapped, and a mutant resistant to degradation was shown to protect cells from apoptosis more efficiently than the wild-type enzyme.
Frutos
S
S
Laboratorio Glaxo Wellcome-CSIC de Biología Molecular y Celular, Centro de Biología Molecular "Severo Ochoa" (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid), Spain.
Moscat
J
J
Diaz-Meco
M T
MT
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014466:Ultraviolet Rays
D007527:Isoenzymes; D011493:Protein Kinase C; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases