2. Academic Validation
  3. ATF7 mediates TNF-α-induced telomere shortening

ATF7 mediates TNF-α-induced telomere shortening

  • Nucleic Acids Res. 2018 May 18;46(9):4487-4504. doi: 10.1093/nar/gky155.
Toshio Maekawa 1,  Binbin Liu 1 2,  Daisuke Nakai 1 2,  Keisuke Yoshida 1,  Ken-Ichi Nakamura 3,  Mami Yasukawa 4,  Manabu Koike 5,  Kaiyo Takubo 3,  Bruno Chatton 6,  Fuyuki Ishikawa 7,  Kenkichi Masutomi 4,  Shunsuke Ishii 1 2
Affiliations

Affiliations

  • 1 Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
  • 2 Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan.
  • 3 Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Sakaecho 35-2, Itabashi-ku, Tokyo 173-0015, Japan.
  • 4 Division of Cancer Stem Cell, National Cancer Center Research Institute, Tokyo, Japan.
  • 5 National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • 6 Université de Strasbourg, UMR7242 Biotechnologie et Signalisation Cellulaire, Ecole Supérieure de Biotechnologie de Strasbourg, BP10413, Illkirch, France.
  • 7 Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
PMID: 29490055 DOI: 10.1093/nar/gky155
Abstract

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.

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