Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1

Polymerase I and transcript release factor (PTRF, also known as Cavin-1) 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.

聚合酶I和转录物释放因子（PTRF，也称为Cavin - 1）是细胞质膜微囊泡（caveolae）生物发生和功能的重要组成部分。在此，我们表明在衰老的人类成纤维细胞中PTRF表达增加。重要的是，PTRF的过表达诱导了细胞衰老的特征，而PTRF表达降低则延长了细胞的复制寿命。有趣的是，我们发现PTRF主要定位于年轻和静止的WI - 38人类成纤维细胞的细胞核，但在细胞衰老过程中转移至细胞质和质膜。此外，电子显微镜分析表明，在衰老的以及转染PTRF的WI - 38细胞中，细胞质膜微囊泡结构的数量增加。我们的数据表明，PTRF在细胞衰老中的作用取决于其靶向细胞质膜微囊泡以及它与小窝蛋白 - 1（caveolin - 1）的相互作用，而这似乎是由PTRF的磷酸化所调控。综上所述，我们的研究结果确定PTRF是一种通过p53 / p21和细胞质膜微囊泡途径起作用的新型细胞衰老调节因子。