Protein kinase C phosphorylates DNA topoisomerase I.
The induction of mammalian cell proliferation requires the expression of a specific set of genes. Tumor promoters stimulate cell growth by activating the Ca2+ and phospholipid-dependent protein kinase, protein kinase C (PKC). DNA topoisomerase I, a nuclear enzyme involved in transcription, was phosphorylated by activated PKC in vitro. Phosphorylation by PKC stimulated the DNA relaxation activity of topoisomerase I two- to three-fold. Therefore, DNA topoisomerase I is a substrate for PKC-mediated activation by phosphorylation and may serve as a nuclear target of mitogenic signals generated by tumor promoters in vivo.
Samuels
D S
DS
Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721.
Shimizu
Y
Y
Shimizu
N
N
D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004278:DNA, Superhelical / Q000378:metabolism; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism*
D004278:DNA, Superhelical; D011493:Protein Kinase C; D004264:DNA Topoisomerases, Type I