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• W2393960714 abstract "Objective To characterize the effects of TPP1 knockdown on Pot1a and Pot1b localization at telomeres and on the telomere end protection.Methods Knockdown of endogenous TPP1 in mouse embryonic fibroblasts(MEFs) with the retrovirus vector encoding shRNA targeting TPP1,IF/PNA-FISH was performed to determine the localization of Pot1a and Pot1b at telomeres,and TdT-FITC was applied to characterize the effects on the function of telomere end protection,cellular senescence was analyzed by SA-beta gal staining,and phosphorylated p53ser18 and p21 were examined by Western blotting.Results Pot1a and Pot1b were unable to localize at telomeres in about 65% of MEFs with TPP1 knockdown,while that was found in less than 5% of MEFs without TPP1 knockdown(t=10.96,P0.01).TdT-FITC positive cells were detected in 50% of TPP1 knockdown MEFs,as compared with that of 4.7% in the control MEFs(t=14.37,P0.01).Furthermore,90% of TdT signals appeared to co-localize with telomeres in TPP1 knockdown cells,which was significantly higher than that of 3% in the control MEFs(t=17.59,P0.01).The SA-beta gal positive cells,a hallmark of cellular senescence,were found in 25.7% and 22.0% of TPP1 knockdown cells by shTPP1-1 or shTPP1-2,paralleled with marked induction of p53ser18 phosphorylation and p21 expression in those cells.Whereas,cellular senescence occurred only in 1.7% of the control MEFs(t=18.23,P0.01;t=16.9,P0.01),and increased p53ser18 phosphorylation and p21 expression were not detected.Conclusion TPP1 is required for Pot1a and Pot1b localization at telomeres,and knockdown of TPP1 results in telomere end accessible and elicits p53-dependent cellular senescence." @default.
• W2393960714 created "2016-06-24" @default.
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• W2393960714 date "2008-01-01" @default.
• W2393960714 modified "2023-09-23" @default.
• W2393960714 title "TPP1 confers telomere end protection by recruiting Pot1a and Pot1b to telomeres" @default.
• W2393960714 hasPublicationYear "2008" @default.
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