共查询到20条相似文献,搜索用时 34 毫秒
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Yuwei Zhang Rodrigo Calado Mahadev Rao Julie A. Hong Alan K. Meeker Bogdan Dumitriu Scott Atay Peter J. McCormick Susan H. Garfield Danny Wangsa Hesed M. Padilla-Nash Sandra Burkett Mary Zhang Tricia F. Kunst Nathan R. Peterson Sichuan Xi Suzanne Inchauste Nasser K. Altorki Alan G. Casson David G. Beer Curtis C. Harris Thomas Ried Neal S. Young David S. Schrump 《PloS one》2014,9(7)
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c-Myc-mediated regulation of telomerase activity is disabled in immortalized cells 总被引:10,自引:0,他引:10
Drissi R Zindy F Roussel MF Cleveland JL 《The Journal of biological chemistry》2001,276(32):29994-30001
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Sang Hyeok Woo Sungkwan An Hyung-Chahn Lee Hyeon-Ok Jin Sung-Keum Seo Doo-Hyun Yoo Kee-Ho Lee Chang Hun Rhee Eui-Ju Choi Seok-Il Hong In-Chul Park 《The Journal of biological chemistry》2009,284(45):30871-30880
The Hsp90-associated protein p23 modulates Hsp90 activity during the final stages of the chaperone pathway to facilitate maturation of client proteins. Previous reports indicate that p23 cleavage induced by caspases during cell death triggers destabilization of client proteins. However, the specific role of truncated p23 (Δp23) in this process and the underlying mechanisms remain to be determined. One such client protein, hTERT, is a telomerase catalytic subunit regulated by several chaperone proteins, including Hsp90 and p23. In the present study, we examined the effects of p23 cleavage on hTERT stability and telomerase activity. Our data showed that overexpression of Δp23 resulted in a decrease in hTERT levels, and a down-regulation in telomerase activity. Serine phosphorylation of Hsp90 was significantly reduced in cells expressing high levels of Δp23 compared with those expressing full-length p23. Mutation analyses revealed that two serine residues (Ser-231 and Ser-263) in Hsp90 are important for activation of telomerase, and down-regulation of telomerase activity by Δp23 was associated with inhibition of cell growth and sensitization of cells to cisplatin. Our data aid in determining the mechanism underlying the regulation of telomerase activity by the chaperone complex during caspase-dependent cell death. 相似文献
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Telomerase catalytic subunit (TERT) seems a key factor controlling telomerase activity, telomere length, and cell growth. To further address this issue, we forced expression of a catalytically inactive mutant human TERT (hTERT) in hTERT-immortalised sheep fibroblasts to examine its effects. Expression of mutant hTERT compromised telomerase activity reconstituted by wild-type hTERT in a manner directly attributable to mutant hTERT expression level. High levels of mutant hTERT expression inhibited cell growth with a subset of cells entering replicative senescence. Furthermore, significant telomere attrition was evident in two of three clones with high levels of mutant hTERT expression. Our findings are consistent with the notion that hTERT homodimers are necessarily required to form a functional telomerase complex at the telomere substrate. We also highlight the requirement of a more thorough understanding of telomerase- and telomere-associated factors to understand fully the interplay that governs telomere homeostasis in vitro and in vivo. 相似文献
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