Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts

Naoko Endo, Etsu Tashiro, Kazuo Umezawa, Manabu Kawada, Yoshimasa Uehara, Yuichiro Doki, I. Bernard Weinstein, Masaya Imoto

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The ansamycin antibiotic herbimycin A is a potent tyrosine kinase inhibitor and reduces the growth rate of various types of mammalian cells. When quiescent Rat6 fibroblast cells were treated with herbimycin A, serum-induced expression of cyclin D1 was inhibited, and this was associated with inhibition of G1 phase progression. However, herbimycin A also inhibited serum-induced G1 progression in derivatives of the Rat6 fibroblast cell line that stably overexpress a human cyclin D1 cDNA (R6ccnD1 4 cells), without affecting the expression levels of G1 cyclins. We found that herbimycin A prevented serum-induced downregulation of the cyclin-dependent kinase inhibitor p27(Kip1), thereby leading to inactivation of the protein kinase activity of CDK2. These results suggest that herbimycin A inhibits a tyrosine kinase(s) that plays a role in degradation of the p27(Kop1) protein. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume267
Issue number1
DOIs
Publication statusPublished - 2000 Jan 7

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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