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M9620576.TXT
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1996-02-26
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Document 0576
DOCN M9620576
TI Inhibition of the association with nuclear matrix of pRB, p70 and p40
proteins along with the specific suppression of c-MYC expression by
geldanamycin, an inhibitor of Src tyrosine kinase.
DT 9602
AU Yamaki H; Nakajima M; Seimiya H; Saya H; Sugita M; Tsuruo T; Institute
of Molecular and Cellular Bioscience, University of; Tokyo, Japan.
SO J Antibiot (Tokyo). 1995 Sep;48(9):1021-6. Unique Identifier : AIDSLINE
MED/96049197
AB Geldanamycin is an antibiotic that preferentially inhibits G1/S
transition and causes G2/M arrest in human leukemia HL-60 cells. With
it, we selectively inhibited recombinant Src tyrosine kinase without
significantly inhibiting protein kinase A. The perturbation of cell
cycling by geldanamycin was accompanied by marked suppression of c-MYC
expression. In contrast to this, pRB expression was remarkably enhanced
by geldanamycin. In the untreated HL-60 cells, c-MYC was apparently
enriched in nuclear matrix preparation, and significant amounts of
hyperphosphorylated pRB, p70 and p40 proteins were observed to
associated with the nuclear matrix. The amounts of these proteins
associated with the nuclear matrix, however, were markedly decreased by
treatment with geldanamycin. This finding suggests that the association
of c-MYC, hyperphosphorylated pRB, p70 and p40 proteins with the nuclear
matrix is essential in cell cycling, especially in G1/S and G2/M
progressions, and that this association is a part of signal transduction
pathway in Src kinase activation.
DE src-Family Kinases/*ANTAGONISTS & INHIB Antibiotics,
Antineoplastic/*PHARMACOLOGY Cell Cycle/DRUG EFFECTS Enzyme
Inhibitors/*PHARMACOLOGY Flow Cytometry Gene Expression
Regulation/DRUG EFFECTS Gene Products, tax/DRUG EFFECTS Genes,
myc/*DRUG EFFECTS Human HL-60 Cells/DRUG EFFECTS Nuclear Matrix/DRUG
EFFECTS Nuclear Proteins/*DRUG EFFECTS Quinones/*PHARMACOLOGY
Retinoblastoma Protein/DRUG EFFECTS Support, Non-U.S. Gov't Tumor
Cells, Cultured/DRUG EFFECTS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).