共查询到20条相似文献,搜索用时 252 毫秒
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Human papillomavirus E2 down-regulates the human telomerase reverse transcriptase promoter 总被引:9,自引:0,他引:9
Lee D Kim HZ Jeong KW Shim YS Horikawa I Barrett JC Choe J 《The Journal of biological chemistry》2002,277(31):27748-27756
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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
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Multiple tumor suppressor pathways negatively regulate telomerase 总被引:26,自引:0,他引:26
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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
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
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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
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Telomerase activity is critical for normal and transformed human cells to escape from crisis and is implicated in oncogenesis. Here we describe a novel Pin2/TRF1 binding protein, PinX1 that inhibits telomerase activity and affects tumorigenicity. PinX1 and its small TID domain bind the telomerase catalytic subunit hTERT and potently inhibit its activity. Overexpression of PinX1 or its TID domain inhibits telomerase activity, shortens telomeres, and induces crisis, whereas depletion of endogenous PinX1 increases telomerase activity and elongates telomeres. Depletion of PinX1 also increases tumorigenicity in nude mice, consistent with its chromosome localization at 8p23, a region with frequent loss of heterozygosity in a number of human cancers. Thus, PinX1 is a potent telomerase inhibitor and a putative tumor suppressor. 相似文献