期刊
ONCOGENE
卷 21, 期 51, 页码 7765-7775出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1205928
关键词
BCL2; BCL-x(L); cell cycle; p27; cdk; Myc
资金
- NCI NIH HHS [T32CA09385, CA58485, R01CA78443] Funding Source: Medline
The anti-apoptotic molecules BCL-X-L and BCL2 delay cell cycle entry from quiescence. We used serum induction and induction of a Myc-estrogen receptor fusion protein (MycER) in quiescent fibroblasts to investigate the mechanisms underlying the cell cycle activity of BCL-X-L and BCL2. We demonstrate for the first time that BCL-x(L) and BCL2 delayed serum-induced and Myc-induced, but not E2F-induced, cell cycle entry. The cyclin-dependent kinase inhibitor p27 was elevated during serum deprivation and cell cycle entry in BCL-X-L or BCL2-expressing NIH3T3 cells and a Rat1MycER cell line. Activation of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4) were delayed during progression to S phase, while the induction of cyclin 131 protein, as well as the levels of cyclin E, cdk2, and cdk4 were unaltered by BCL-X-L or BCL2. Inhibition of cyclin/cdk activities in BCL-X-L or BCL2 expressing cells was associated with excess p27 in the cyclin/cdk complexes. Neither BCL-X-L nor BCL2 delayed S phase entry in cells deficient in p27, thus p27 is required for the cell cycle function of BCL-X-L and BCL2. The cell cycle effects of BCL-X-L and BCL2 were more profound in Myc-induced than in serum-induced cell cycle entry. Our results suggest that one possible mechanism by which BCL-X-L and BCL2 delay cell cycle entry may be the inhibition of Myc activity through the elevation of p27.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据