Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Ann N Y Acad Sci. 2010 Jun;1197:134-41. doi: 10.1111/j.1749-6632.2010.05197.x.
Cellular senescence is the dominant phenotype over immortality. In our studies to identify senescence-related genes, we cloned Morf4, which induced senescence in a subset of tumor cells. Morf4 is a member of a family of seven genes, and Morf-related genes (Mrg) on chromosomes 15 (Mrg15) and X (MrgX) are also expressed. In contrast to MORF4, MRG15 and MRGX are positive regulators of cell division. All three proteins interact with histone deacetylases and acetyltransferases, suggesting that they function in regulation of chromatin dynamics. Mrg15 knockout mice are embryonic lethal, and mouse embryonic fibroblasts derived from Mrg15 null embryos proliferate poorly, enter senescence rapidly, and have impaired DNA repair compared to the wild type. Mrg15 null embryonic neural stem and progenitor cells also have a decreased capacity for proliferation and differentiation. Further studies are needed to determine the function of this gene family in various biological processes, including neural stem and progenitor cell aging.
细胞衰老（cellular senescence）是一种超越永生（immortality）的主导表型。在我们鉴定与衰老相关基因的研究中，克隆了诱导部分肿瘤细胞衰老的 Morf4。Morf4 是一个包含 7 个基因的家族的成员，染色体 15（Mrg15）和 X 上的 Morf 相关基因（MrgX）也有表达。与 MORF4 相反，MRG15 和 MRGX 是细胞分裂的正向调节因子。这三种蛋白质都与组蛋白去乙酰化酶和乙酰转移酶相互作用，表明它们在调节染色质动力学方面发挥作用。Mrg15 敲除小鼠是胚胎致死的，而源自 Mrg15 缺失胚胎的小鼠胚胎成纤维细胞增殖能力差，迅速进入衰老状态，与野生型相比，其 DNA 修复能力受损。Mrg15 缺失的胚胎神经干细胞和祖细胞的增殖和分化能力也降低。需要进一步研究以确定该基因家族在包括神经干细胞和祖细胞衰老在内的各种生物学过程中的功能。
