Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73

• Masataka Hoshino

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Mei-ling Qi

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Natsue Yoshimura

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Tomoyuki Miyashita

  2Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan

• Kazuhiko Tagawa

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Yo-ichi Wada

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Yasushi Enokido

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Shigeki Marubuchi

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

• Phoebe Harjes

  3Neuroproteomics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany

• Nobutaka Arai

  2Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan

• Kiyomitsu Oyanagi

  2Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan

• Giovanni Blandino

  4Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy

• Marius Sudol

  5Weis Center for Research, Geisinger Clinic, Danville, PA 17822

• Tina Rich

  6Department of Pathology, University of Cambridge, Cambridge CB2 1QP, England, UK

• Ichiro Kanazawa

  7National Center for Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan

• Erich E. Wanker

  3Neuroproteomics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany

• Minoru Saitoe

  2Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan

• Hitoshi Okazawa

  1Department of Neuropathology, Medical Research Institute and Center of Excellence Program for Brain Integration and Its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

抄録

Transcriptional disturbance is implicated in the pathology of polyglutamine diseases, including Huntington's disease (HD). However, it is unknown whether transcriptional repression leads to neuronal death or what forms that death might take. We found transcriptional repression-induced atypical death (TRIAD) of neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of TRIAD was extremely slow in comparison with other types of cell death. Gene expression profiling revealed the reduction of full-length yes-associated protein (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore, novel neuron-specific YAP isoforms (YAPΔCs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAPΔCs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAPΔCs also markedly attenuated Htt-induced neuronal death in primary neuron and Drosophila melanogaster models. Collectively, transcriptional repression induces a novel prototype of neuronal death associated with the changes of YAP isoforms and p73, which might be relevant to the HD pathology.

収録刊行物

• The Journal of Cell Biology

  The Journal of Cell Biology 172 (4), 589-604, 2006-02-06

  Rockefeller University Press

キーワード

• Cell Biology

詳細情報

• CRID: 1360292621285037056
• NII論文ID: 80019302206
• DOI: 10.1083/jcb.200509132
• ISSN: 15408140
• ISSN: 00219525
• ISSN: http://id.crossref.org/issn/00219525
• Web Site: https://rupress.org/jcb/article-pdf/172/4/589/1872764/589.pdf
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