Communications Biology (Oct 2021)
HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer’s disease pathology
- Hikari Tanaka,
- Kanoh Kondo,
- Kyota Fujita,
- Hidenori Homma,
- Kazuhiko Tagawa,
- Xiaocen Jin,
- Meihua Jin,
- Yuki Yoshioka,
- Sumire Takayama,
- Hitomi Masuda,
- Rie Tokuyama,
- Yukoh Nakazaki,
- Takashi Saito,
- Takaomi Saido,
- Shigeo Murayama,
- Teikichi Ikura,
- Nobutoshi Ito,
- Yu Yamamori,
- Kentaro Tomii,
- Marco E. Bianchi,
- Hitoshi Okazawa
Affiliations
- Hikari Tanaka
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Kanoh Kondo
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Kyota Fujita
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Hidenori Homma
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Kazuhiko Tagawa
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Xiaocen Jin
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Meihua Jin
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Yuki Yoshioka
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Sumire Takayama
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- Hitomi Masuda
- Chiome Bioscience, Inc.
- Rie Tokuyama
- Chiome Bioscience, Inc.
- Yukoh Nakazaki
- Chiome Bioscience, Inc.
- Takashi Saito
- Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences
- Takaomi Saido
- Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science
- Shigeo Murayama
- Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology
- Teikichi Ikura
- Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University
- Nobutoshi Ito
- Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University
- Yu Yamamori
- Intelligent Bioinformatics Research Team, Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology
- Kentaro Tomii
- Intelligent Bioinformatics Research Team, Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology
- Marco E. Bianchi
- Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute
- Hitoshi Okazawa
- Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
- DOI
- https://doi.org/10.1038/s42003-021-02671-4
- Journal volume & issue
-
Vol. 4,
no. 1
pp. 1 – 23
Abstract
Tanaka et al use phosphoproteome analysis of post-mortem Alzheimer’s Disease (AD) brains and identified abnormal phosphorylation of Ku70, which leads to DNA damage and transcriptional repression-induced atypical cell death. In a mouse model of AD, the authors show that Ku70 phosporylation is regulated by extracellular high mobility group box 1 protein, thus shedding light on the mechanism of DNA damage in AD.
