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作 者:Lin Bai Xiaoli Deng Juanjuan Li Miao Wang Qian Li Wei An Deli A Yu-Sheng Cong
出 处:《Cell Research》2011年第7期1088-1101,共14页细胞研究(英文版)
基 金:thank Dr Silvia Bacchetti for critical reading of the manuscript, Dr Pingsheng Liu for providing the caveolin-I siRNA and helpful discussions. This work was supported in part by a grant from the National Natural Science Foundation of China (30671065) and grants from the National Basic Research Program of China (973 Program) (2007CB507402, 2007CB914402).
摘 要:Polymerase I and transcript release factor (PTRF, also known as Cavin-l) is an essential component in the biogenesis and function of caveolae. Here, we show that PTRF expression is increased in senescent human fibroblasts. Importantly, overexpression of PTRF induced features characteristic of cellular senescence, whereas reduced PTRF expression extended the cellular replicative lifespan. Interestingly, we found that PTRF localized primarily to the nuclei of young and quiescent WI-38 human fibroblasts, but translocated to the cytosol and plasma membrane during cellular senescence. Furthermore, electron microscopic analysis demonstrated an increased number of caveolar structures in senescent and PTRF-transfected WI-38 cells. Our data suggest that the role of PTRF in cellular senescence is dependent on its targeting to caveolae and its interaction with caveolin-1, which appeared to be regulated by the phosphorylation of PTRF. Taken together, our findings identify PTRF as a novel regulator of cellular senescence that acts through the p53/p21 and caveolar pathways.
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