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

Fingerprint

Cyclin D1
Fibroblasts
Cells
Protein-Tyrosine Kinases
Serum
Cyclin G1
Rifabutin
Cyclin-Dependent Kinase Inhibitor p27
Growth Inhibitors
G1 Phase
Protein Kinases
Down-Regulation
Complementary DNA
herbimycin
Anti-Bacterial Agents
Derivatives
Cell Line
Degradation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts. / Endo, Naoko; Tashiro, Etsu; Umezawa, Kazuo; Kawada, Manabu; Uehara, Yoshimasa; Doki, Yuichiro; Weinstein, I. Bernard; Imoto, Masaya.

In: Biochemical and Biophysical Research Communications, Vol. 267, No. 1, 07.01.2000, p. 54-58.

Research output: Contribution to journalArticle

Endo, Naoko ; Tashiro, Etsu ; Umezawa, Kazuo ; Kawada, Manabu ; Uehara, Yoshimasa ; Doki, Yuichiro ; Weinstein, I. Bernard ; Imoto, Masaya. / Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 267, No. 1. pp. 54-58.
@article{dd4037fbf58940f99342cf4630e91d61,
title = "Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts",
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.",
author = "Naoko Endo and Etsu Tashiro and Kazuo Umezawa and Manabu Kawada and Yoshimasa Uehara and Yuichiro Doki and Weinstein, {I. Bernard} and Masaya Imoto",
year = "2000",
month = "1",
day = "7",
doi = "10.1006/bbrc.1999.1927",
language = "English",
volume = "267",
pages = "54--58",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Herbimycin A induces G1 arrest through accumulation of p27(Kip1) in cyclin D1-overexpressing fibroblasts

AU - Endo, Naoko

AU - Tashiro, Etsu

AU - Umezawa, Kazuo

AU - Kawada, Manabu

AU - Uehara, Yoshimasa

AU - Doki, Yuichiro

AU - Weinstein, I. Bernard

AU - Imoto, Masaya

PY - 2000/1/7

Y1 - 2000/1/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034614431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034614431&partnerID=8YFLogxK

U2 - 10.1006/bbrc.1999.1927

DO - 10.1006/bbrc.1999.1927

M3 - Article

C2 - 10623573

AN - SCOPUS:0034614431

VL - 267

SP - 54

EP - 58

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -