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 language | English |
|---|---|
| Pages (from-to) | 54-58 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 267 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2000 Jan 7 |
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ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
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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 journal › Article
}
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.
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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 -