衰老中的 Gadd45。
Gadd45 in Senescence.
机构信息
Fels Cancer Institute for Personalized Medicine, Department of Cancer and Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
出版信息
Adv Exp Med Biol. 2022;1360:109-116. doi: 10.1007/978-3-030-94804-7_8.
Abstract
Gadd45a, Gadd45b, and Gadd45g have been implicated in cell cycle arrest, DNA repair, apoptosis, innate immunity, genomic stability, and more recently in senescence. Evidence has accumulated that Gadd45a deficiency results in escape of mouse embryo fibroblasts from senescence, whereas Gadd45b deficiency promotes premature senescence and skin aging. Moreover, recently Gadd45b deficiency was found to promote senescence and attenuate liver fibrosis, whereas Gadd45a was observed to exert a protective effect against hepatic fibrosis. These findings indicate that the Gadd45 stress response proteins play important roles in modulating cellular responses to senescence. Thus, exploring how Gadd45 proteins modulate cellular senescence has the potential to provide new and innovative tools to treat cancer as well as liver disease.
摘要
Gadd45a、Gadd45b 和 Gadd45g 被认为参与细胞周期阻滞、DNA 修复、细胞凋亡、固有免疫、基因组稳定性，以及最近的衰老过程。有证据表明，Gadd45a 缺乏会导致小鼠胚胎成纤维细胞逃避衰老，而 Gadd45b 缺乏则会促进过早衰老和皮肤老化。此外，最近的研究发现 Gadd45b 缺乏会促进衰老和肝纤维化，而 Gadd45a 则被观察到对肝纤维化具有保护作用。这些发现表明，Gadd45 应激反应蛋白在调节细胞对衰老的反应中发挥重要作用。因此，探索 Gadd45 蛋白如何调节细胞衰老，有可能为治疗癌症和肝脏疾病提供新的、创新的工具。
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Biochim Biophys Acta Mol Basis Dis. 2017 Dec;1863(12):3170-3182. doi: 10.1016/j.bbadis.2017.08.017. Epub 2017 Aug 24.
2
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3
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