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[Cancer Research 63, 1153-1156, March 15, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Phospholipid Scramblase 3 Is the Mitochondrial Target of Protein Kinase C {delta}-induced Apoptosis1

Jihua Liu, Jun Chen, Qiang Dai and Ray M. Lee2

Huntsman Cancer Institute and Section of Oncology, Department of Medicine, University of Utah, Salt Lake City, Utah 84112

Protein kinase C (PKC) {delta} translocates to mitochondria during apo-ptosis,but its mitochondrial target remains unclear. We found that PKC-{delta} physically interacted with and phosphorylated phospholipid scramblase 3 (PLS3) after UV irradiation. PLS3 is a high-affinity substrate for PKC-{delta} in vitro with the Km at 10.5 nM. Cells expressing wild-type PLS3 became apoptotic on phorbol ester stimulation, whereas the control cells did not. Expression of a mitochondrial-targeted PKC-{delta} enhanced apoptosis more prominently in HeLa-PLS3 cells than control HeLa cells and HeLa cells expressing an inactive PLS3 mutant. These results indicate that PLS3 is a downstream effector of PKC-{delta} in the mitochondria.




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