       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).

