Phosphorylation of topoisomerase I in L5178Y-S cells is associated with poly(ADP-ribose) metabolism.

Abstract:

: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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Staron K,Kowalska-Loth B,Nieznanski K,Szumiel I

doi

10.1093/carcin/17.3.383

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

383-7

issue

3

eissn

0143-3334

issn

1460-2180

journal_volume

17

pub_type

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