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