JCB logo
BD Biosciences
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 6 February 2006. doi:10.1083/jcb.200509132
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 4, 589-604
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hoshino, M.
Right arrow Articles by Okazawa, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hoshino, M.
Right arrow Articles by Okazawa, H.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

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

Masataka Hoshino1, Mei-ling Qi1, Natsue Yoshimura1, Tomoyuki Miyashita2, Kazuhiko Tagawa1, Yo-ichi Wada1, Yasushi Enokido1, Shigeki Marubuchi1, Phoebe Harjes3, Nobutaka Arai2, Kiyomitsu Oyanagi2, Giovanni Blandino4, Marius Sudol5, Tina Rich6, Ichiro Kanazawa7, Erich E. Wanker3, Minoru Saitoe2, and Hitoshi Okazawa1,2,8

1 Department 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
2 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan
3 Neuroproteomics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
4 Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy
5 Weis Center for Research, Geisinger Clinic, Danville, PA 17822
6 Department of Pathology, University of Cambridge, Cambridge CB2 1QP, England, UK
7 National Center for Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
8 Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawagoe, Saitama 332-0012, Japan

Correspondence to Hitoshi Okazawa: okazawa-tky{at}umin.ac.jp

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 (YAP{Delta}Cs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAP{Delta}Cs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAP{Delta}Cs 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.

Abbreviations used in this paper: AMA, {alpha}-amanitin; CDDP, cisplatin; FL-YAP, full-length YAP; HD, Huntington's disease; Pol II, polymerase II; polyQ, polyglutamine; siRNA, short inhibitory RNA; TRIAD, transcriptional repression-induced atypical death; YAP, yes-associated protein.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

A slow death
Rabiya S. Tuma
J. Cell Biol. 2006 172: 481. [Full Text]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents