Phosphorylation of topoisomerase I in L5178Y-S cells is associated with poly(ADP-ribose) metabolism.
The reason for different phosphorylation of topoisomerase I in two sublines of L5178Y murine lymphoma (LY cells) was investigated. Camptothecin-resistant LY-S cells show increased poly(ADP-ribose) level and lowered topoisomerase I phosphorylation compared to camptothecin-sensitive LY-R cells. In this study diminished phosphorylation of LY-S topoisomerase I was observed for sites recognized by casein kinase 2 but not for those phosphorylated by protein kinase C. Tryptic digests of LY-S topoisomerase I labeled in vitro by casein kinase 2 indicated that phosphorylation was similarly lowered at different sites. Activity of casein kinase 2 measured in nuclear extracts was about 1.7 times lower for LY-S than LY-R cells. This difference was diminished or eliminated by increasing casein concentration, diluting the extract or increasing the ionic strength. Activity of poly(ADP-ribose) polymerase was 5.3 times higher in LY-S than in LY-R nuclei. When the activity of the polymerase was inhibited by treatment of LY-S cells with benzamide, casein kinase 2-catalyzed phosphorylation of topoisomerase I increased. This was accompanied by an increase in sensitivity to camptothecin as reflected in the diminished viability of LY-S cells.
Staron
K
K
Institute of Biochemistry, Warsaw University, Poland.
Kowalska-Loth
B
B
Nieznanski
K
K
Szumiel
I
I
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D047390:Casein Kinase II; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004347:Drug Interactions; D007940:Leukemia L5178 / Q000201:enzymology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D001549:Benzamides; C037689:benzamide; D011065:Poly(ADP-ribose) Polymerases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin