Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-2-15
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1350-9047
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
224-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15618968-Apoptosis, pubmed-meshheading:15618968-Caspase 3, pubmed-meshheading:15618968-Caspases, pubmed-meshheading:15618968-Catalytic Domain, pubmed-meshheading:15618968-Cell Survival, pubmed-meshheading:15618968-Cells, Cultured, pubmed-meshheading:15618968-Cytochromes c, pubmed-meshheading:15618968-Down-Regulation, pubmed-meshheading:15618968-Enzyme Activation, pubmed-meshheading:15618968-Flow Cytometry, pubmed-meshheading:15618968-Humans, pubmed-meshheading:15618968-Keratinocytes, pubmed-meshheading:15618968-Membrane Potentials, pubmed-meshheading:15618968-Mitochondria, pubmed-meshheading:15618968-Mutation, pubmed-meshheading:15618968-Neoplasm Proteins, pubmed-meshheading:15618968-Protein Kinase C, pubmed-meshheading:15618968-Protein Kinase C-delta, pubmed-meshheading:15618968-Protein Transport, pubmed-meshheading:15618968-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:15618968-Ultraviolet Rays
pubmed:year
2005
pubmed:articleTitle
A caspase-resistant mutant of PKC-delta protects keratinocytes from UV-induced apoptosis.
pubmed:affiliation
Division of Molecular and Cellular Biochemistry, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural