Abstract
Protein kinase C (PKC) fulfills a central role in the decision of cell fate in keratinocytes. Both PKCδ and PKCη induce growth inhibition and differentiation of normal human keratinocytes (NHK). Here we show that PKCδ and PKCη play opposite roles in UVB-induced apoptosis in NHK. PKCδ enhanced UVB-induced caspase-3 activity, while overexpression of PKCη reduced it. In keeping with these observations, the dominant negative mutant of PKCδ significantly inhibited the activation of caspase-3, whereas dominant negative PKCη increased it in a dose (MOI)-dependent manner. Unlike PKCδ, cleavage and translocation to mitochondria of PKCη 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 PKCη. These findings suggest that PKCη negatively regulates UV-induced apoptosis through its localization, resistance to cleavage, and the p38 MAPK pathway.
Published Version
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