Pontin, a member of the AAA+ ATPase family, plays important roles in a variety of cellular processes, including transcription regulation, DNA damage response, telomerase activity, and cellular transformation. In the previous studies, Pontin deletion in mice was lethal to embryos. Here, we demonstrate that the depletion of Pontin induced cellular senescence in mouse and human fibroblasts as well as in mouse epidermal keratinocytes. Fibroblast cells with Pontin depletion exhibited a defect in cell proliferation without showing apoptosis. Instead, they exhibited senescence-associated phenotypes including increased senescence-associated-β-galactosidase activity, elevated levels of p16INK4, and senescence-associated secretory phenotypes. Furthermore, conditional deletion of the Pontin gene in epidermal keratinocytes led to abnormal epidermal stratification, which was accompanied by the induction of senescence in Pontin-lacking cells. We found that Pontin depletion induced a spontaneous DNA damage response, which may be a cause of senescence. Contrary to the behavior of normal cells, Pontin depletion in several cancer cells caused apoptotic cell death without exhibiting senescence phenotypes.

中文翻译：

---

桥蛋白缺乏导致成纤维细胞和表皮角质形成细胞衰老，但诱导癌细胞凋亡。

Pontin是AAA + ATPase家族的成员，在多种细胞过程中发挥重要作用，包括转录调控，DNA损伤反应，端粒酶活性和细胞转化。在以前的研究中，小鼠的Pontin缺失对胚胎具有致命性。在这里，我们证明了在小鼠和人类成纤维细胞以及小鼠表皮角质形成细胞中，Pontin的缺失诱导了细胞衰老。具有庞廷蛋白耗竭的成纤维细胞在细胞增殖中表现出缺陷，而未显示出凋亡。相反，他们表现出与衰老相关的表型，包括衰老相关的β-半乳糖苷酶活性增加，p16INK4水平升高和衰老相关的分泌表型。此外，表皮角质形成细胞中Pontin基因的条件性缺失会导致表皮分层异常，并伴随缺少Pontin的细胞的衰老诱导。我们发现，Pontin耗竭诱导了自发的DNA损伤反应，这可能是衰老的原因。与正常细胞的行为相反，几种癌细胞中的Pontin耗竭导致凋亡性细胞死亡，而没有表现出衰老表型。