The eta isoform of protein kinase C inhibits UV-induced activation of caspase-3 in normal human keratinocytes.
Protein kinase C (PKC) fulfills a central role in the decision of cell fate in keratinocytes. Both PKC delta and PKC eta induce growth inhibition and differentiation of normal human keratinocytes (NHK). Here we show that PKC delta and PKC eta play opposite roles in UVB-induced apoptosis in NHK. PKC delta enhanced UVB-induced caspase-3 activity, while overexpression of PKC eta reduced it. In keeping with these observations, the dominant negative mutant of PKC delta significantly inhibited the activation of caspase-3, whereas dominant negative PKC eta increased it in a dose (MOI)-dependent manner. Unlike PKC delta, cleavage and translocation to mitochondria of PKC eta were not observed, resulting in no detection of cytochorome c release. Furthermore, UV-induced activation of p38 MAP kinase, which suppressed the caspase-3 activity in NHK, was blocked by dominant negative PKC eta. These findings suggest that PKC eta negatively regulates UV-induced apoptosis through its localization, resistance to cleavage, and the p38 MAPK pathway.
Matsumura
Miyoko
M
Institute of Molecular Oncology, Showa University, Shinagawa-ku, Tokyo 142-8555, Japan.
Tanaka
Naoya
N
Kuroki
Toshio
T
Ichihashi
Masamitsu
M
Ohba
Motoi
M
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005799:Genes, Dominant; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism; D051745:Protein Kinase C-delta; D013347:Subcellular Fractions; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; C081975:protein kinase C eta; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases