INHIBITION OF THE ASSOCIATION WITH NUCLEAR MATRIX OF PRB, P70 AND P40PROTEINS ALONG WITH THE SPECIFIC SUPPRESSION OF C-MYC EXPRESSION BY GELDANAMYCIN, AN INHIBITOR OF SRC TYROSINE KINASE
H. Yamaki et al., INHIBITION OF THE ASSOCIATION WITH NUCLEAR MATRIX OF PRB, P70 AND P40PROTEINS ALONG WITH THE SPECIFIC SUPPRESSION OF C-MYC EXPRESSION BY GELDANAMYCIN, AN INHIBITOR OF SRC TYROSINE KINASE, Journal of antibiotics, 48(9), 1995, pp. 1021-1026
Geldanamycin is an antibiotic that preferentially inhibits G1/S transi
tion and causes G2/M arrest in human leukemia HL-60 cells. With it, we
selectively inhibited recombinant Src tyrosine kinase without signifi
cantly inhibiting protein kinase A. The perturbation of cell cycling b
y geldanamycin was accompanied by marked suppression of c-MYC expressi
on. In contrast to this, pRB expression was remarkably enhanced by gel
danamycin. In the untreated HL-60 cells, c-MYC was apparently enriched
in nuclear matrix preparation, and significant amounts of hyperphosph
orylated pRB, p70 and p40 proteins were observed to associate with the
nuclear matrix. The amounts of these proteins associated with the nuc
lear matrix, however, were markedly decreased by treatment with geldan
amycin. This finding suggests that the association of c-MYC, hyperphos
phorylated pRB, p70 and p40 proteins with the nuclear matrix is essent
ial in cell cycling, especially in G1/S and G2/M progressions, and tha
t this association is a part of signal transduction pathway in Src kin
ase activation.