ALTERATION OF THE PHOSPHORYLATION STATE OF P34(CDC2) KINASE BY THE FLAVONE L86-8275 IN BREAST-CARCINOMA CELLS - CORRELATION WITH DECREASED H1 KINASE-ACTIVITY

Citation
Pj. Worland et al., ALTERATION OF THE PHOSPHORYLATION STATE OF P34(CDC2) KINASE BY THE FLAVONE L86-8275 IN BREAST-CARCINOMA CELLS - CORRELATION WITH DECREASED H1 KINASE-ACTIVITY, Biochemical pharmacology, 46(10), 1993, pp. 1831-1840
Citations number
27
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
46
Issue
10
Year of publication
1993
Pages
1831 - 1840
Database
ISI
SICI code
0006-2952(1993)46:10<1831:AOTPSO>2.0.ZU;2-B
Abstract
The flavone L86-8275 roxy-1-methyl)-piperidinyl]-4H-1-benzopyran-4-one ] delayed the progression of aphidicolin-synchronized MDA-468 breast c arcinoma cells through S phase and prevented progression through G2. L 86-8275 prevented the G2-related increase in histone HI kinase activit y mediated by cyclin-dependent kinase-1 (p34cdc2 kinase). L86-8275 inh ibited [P-32]orthophosphate labeling of p34cdc2 threonine and tyrosine residues and decreased the phosphotyrosine content of p34cdc2. Diminu tion of p34cdc2 phosphotyrosine appeared selective, as a general deple tion of cellular phosphotyrosine was not observed. The mass of p34cdc2 in L86-8275-exposed cells was not decreased during the period over wh ich these effects occurred. [S-35]Methionine labeling of p34cdc2 or ot her cellular proteins was not inhibited at concentrations that were ef fective for complete cellular growth inhibition. We hypothesize that L 86-8275 interferes with the normal cell cycle-dependent phosphorylatio n of p34cdc2, resulting in decreased kinase activity and cell cycle ar rest.