A caspase-resistant mutant of PKC-δ protects keratinocytes from UV-induced apoptosis
A caspase-resistant mutant of PKC-δ protects keratinocytes from UV-induced apoptosis
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DOI：
10.1038/sj.cdd.4401558
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发表时间：
2005-03-01
影响因子：
12.4
通讯作者：
Denning, MF
中科院分区：
文献类型：
--
作者：
D'Costa, AM;Denning, MF
Keratinocyte apoptosis induced by UV radiation is a major protective mechanism from skin photocarcinogenesis. The induction of apoptosis by UV radiation, as well as a variety of genotoxic stimuli, involves the activation of PKC-delta by caspase-3-mediated cleavage in its hinge region, thus generating a constitutively active catalytic fragment. To determine the role of PKC-delta cleavage in UV apoptosis signaling, we introduced a caspase-resistant PKC-delta mutant (D330A) into human keratinocytes by retrovirus transduction. Overexpression of PKC-delta( D330A) protected keratinocytes from UV-induced apoptosis and enhanced long-term survival. PKC-delta( D330A) partially prevented the release of cytochrome c from the mitochondria and the loss of Mcl-1, a key antiapoptotic protein downregulated during UV apoptosis. Thus, the cleavage and activation of PKC-delta are critical components of UV-induced apoptosis in human keratinocytes, and the inactivation of PKC-delta can promote the survival of keratinocytes exposed to UV radiation.
