Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan.
Nucleic Acids Res. 2018 May 18;46(9):4487-4504. doi: 10.1093/nar/gky155.
Telomeres maintain the integrity of chromosome ends and telomere length is an important marker of aging. The epidemiological studies suggested that many types of stress including psychosocial stress decrease telomere length. However, it remains unknown how various stresses induce telomere shortening. Here, we report that the stress-responsive transcription factor ATF7 mediates TNF-α-induced telomere shortening. ATF7 and telomerase, an enzyme that elongates telomeres, are localized on telomeres via interactions with the Ku complex. In response to TNF-α, which is induced by various stresses including psychological stress, ATF7 was phosphorylated by p38, leading to the release of ATF7 and telomerase from telomeres. Thus, a decrease of ATF7 and telomerase on telomeres in response to stress causes telomere shortening, as observed in ATF7-deficient mice. These findings give credence to the idea that various types of stress might shorten telomere.
端粒维持染色体末端的完整性，端粒长度是衰老的一个重要标志物。流行病学研究表明，包括心理社会压力在内的许多类型的压力都会导致端粒缩短。然而，目前尚不清楚各种压力是如何诱导端粒缩短的。在这里，我们报告应激反应转录因子 ATF7 介导 TNF-α诱导的端粒缩短。ATF7 和端粒酶是一种延长端粒的酶，通过与 Ku 复合物相互作用定位于端粒上。在各种应激（包括心理应激）诱导的 TNF-α的作用下，p38 使 ATF7 磷酸化，导致 ATF7 和端粒酶从端粒上释放。因此，应激反应导致端粒上的 ATF7 和端粒酶减少，从而导致端粒缩短，这在 ATF7 缺陷小鼠中得到了观察。这些发现为各种类型的应激可能会缩短端粒的观点提供了依据。
Zotero 插件
