共查询到20条相似文献,搜索用时 31 毫秒
1.
2.
3.
p53-dependent down-regulation of telomerase is mediated by p21waf1 总被引:13,自引:0,他引:13
Shats I Milyavsky M Tang X Stambolsky P Erez N Brosh R Kogan I Braunstein I Tzukerman M Ginsberg D Rotter V 《The Journal of biological chemistry》2004,279(49):50976-50985
4.
5.
The oncogenic process often leads to a loss of normal telomere length control, usually as a result of activation of telomerase. Nevertheless, there are also telomerase-independent events that involve a Rad50-dependent recombination mechanism to maintain telomere length. Previous work has implicated the Rb family of proteins in the control of telomere length, and we now demonstrate that the p130 member of the Rb family is critical for telomere length control. p130 interacts specifically with the RINT-1 protein, previously identified as a Rad50-interacting protein. We further show that RINT-1 is essential for telomere length control. We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells. Given previous work implicating E2F in the control of telomerase gene expression, these results thus point to complementary roles for the Rb/E2F pathway in the control of telomere length. 相似文献
6.
Rb and E2F-1 regulate telomerase activity in human cancer cells 总被引:10,自引:0,他引:10
7.
8.
Repression of the human papillomavirus E6 gene initiates p53-dependent, telomerase-independent senescence and apoptosis in HeLa cervical carcinoma cells 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins. When both HPV oncogenes are repressed in HeLa cervical carcinoma cells, the dormant p53 and retinoblastoma (Rb) tumor suppressor pathways are activated, and the cells undergo senescence in the absence of apoptosis. When the E6 gene is repressed in cells that continue to express an E7 gene, the p53 pathway, but not the Rb pathway, is activated, and both senescence and apoptosis are triggered. To determine the role of p53 signaling in senescence or apoptosis after repression of HPV oncogenes, we introduced a dominant-negative allele of p53 into HeLa cells. Dominant-negative p53 prevented senescence and apoptosis when E6 alone was repressed but did not inhibit senescence when both E6 and E7 were repressed. To determine whether reduced telomerase activity was involved in senescence or apoptosis after E6 repression, we generated HeLa cells stably expressing an exogenous hTERT gene, which encodes the catalytic subunit of telomerase. Although these cells contained markedly elevated telomerase activity and elongated telomeres, hTERT expression did not prevent senescence and apoptosis when E6 alone was repressed. These results demonstrate that when the Rb tumor suppressor pathway is inactivated by the E7 protein, E6 repression activates p53 signaling, which in turn is required for growth inhibition, senescence, and apoptosis. Thus, sustained inactivation of the p53 pathway by the E6 protein is required for maintenance of the proliferative phenotype of HeLa cervical carcinoma cells. 相似文献
9.
10.
11.
12.
13.
Raloxifene inhibits estrogen-induced up-regulation of telomerase activity in a human breast cancer cell line 总被引:10,自引:0,他引:10
Kawagoe J Ohmichi M Takahashi T Ohshima C Mabuchi S Takahashi K Igarashi H Mori-Abe A Saitoh M Du B Ohta T Kimura A Kyo S Inoue M Kurachi H 《The Journal of biological chemistry》2003,278(44):43363-43372
14.
15.
16.
17.
18.
19.
Multiple tumor suppressor pathways negatively regulate telomerase 总被引:26,自引:0,他引:26
20.