The protein kinase Cdelta catalytic fragment is critical for maintenance of the G2/M DNA damage checkpoint.

The Journal of Biological Chemistry
Edward L LaGoryM F Denning

Abstract

Protein kinase Cdelta (PKCdelta) is an essential component of the intrinsic apoptotic program. Following DNA damage, such as exposure to UV radiation, PKCdelta is cleaved in a caspase-dependent manner, generating a constitutively active catalytic fragment (PKCdelta-cat), which is necessary and sufficient for keratinocyte apoptosis. We found that in addition to inducing apoptosis, expression of PKCdelta-cat caused a pronounced G(2)/M cell cycle arrest in both primary human keratinocytes and immortalized HaCaT cells. Consistent with a G(2)/M arrest, PKCdelta-cat induced phosphorylation of Cdk1 (Tyr(15)), a critical event in the G(2)/M checkpoint. Treatment with the ATM/ATR inhibitor caffeine was unable to prevent PKCdelta-cat-induced G(2)/M arrest, suggesting that PKCdelta-cat is functioning downstream of ATM/ATR in the G(2)/M checkpoint. To better understand the role of PKCdelta and PKCdelta-cat in the cell cycle response to DNA damage, we exposed wild-type and PKCdelta null mouse embryonic fibroblasts (MEFs) to UV radiation. Wild-type MEFs underwent a pronounced G(2)/M arrest, Cdk1 phosphorylation, and induction of apoptosis following UV exposure, whereas PKCdelta null MEFs were resistant to these effects. Expression of PKCdelt...Continue Reading

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Citations

Apr 2, 2011·The Journal of Biological Chemistry·HongBin WangMarcelo G Kazanietz
Mar 6, 2013·Molecular & Cellular Proteomics : MCP·Koshi ImamiLeonard J Foster
Aug 25, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Meng ZhaoGuo-Qiang Chen
Aug 30, 2012·Protein Science : a Publication of the Protein Society·Alexander Varshavsky
Oct 12, 2020·Advances in Biological Regulation·Peter J Parker Silvia Martini

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