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Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063678/ https://www.ncbi.nlm.nih.gov/pubmed/16461361 http://dx.doi.org/10.1083/jcb.200509132 |
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author | Hoshino, Masataka Qi, Mei-ling Yoshimura, Natsue Miyashita, Tomoyuki Tagawa, Kazuhiko Wada, Yo-ichi Enokido, Yasushi Marubuchi, Shigeki Harjes, Phoebe Arai, Nobutaka Oyanagi, Kiyomitsu Blandino, Giovanni Sudol, Marius Rich, Tina Kanazawa, Ichiro Wanker, Erich E. Saitoe, Minoru Okazawa, Hitoshi |
author_facet | Hoshino, Masataka Qi, Mei-ling Yoshimura, Natsue Miyashita, Tomoyuki Tagawa, Kazuhiko Wada, Yo-ichi Enokido, Yasushi Marubuchi, Shigeki Harjes, Phoebe Arai, Nobutaka Oyanagi, Kiyomitsu Blandino, Giovanni Sudol, Marius Rich, Tina Kanazawa, Ichiro Wanker, Erich E. Saitoe, Minoru Okazawa, Hitoshi |
author_sort | Hoshino, Masataka |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2063678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20636782007-11-29 Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 Hoshino, Masataka Qi, Mei-ling Yoshimura, Natsue Miyashita, Tomoyuki Tagawa, Kazuhiko Wada, Yo-ichi Enokido, Yasushi Marubuchi, Shigeki Harjes, Phoebe Arai, Nobutaka Oyanagi, Kiyomitsu Blandino, Giovanni Sudol, Marius Rich, Tina Kanazawa, Ichiro Wanker, Erich E. Saitoe, Minoru Okazawa, Hitoshi J Cell Biol Research Articles 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. The Rockefeller University Press 2006-02-13 /pmc/articles/PMC2063678/ /pubmed/16461361 http://dx.doi.org/10.1083/jcb.200509132 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Hoshino, Masataka Qi, Mei-ling Yoshimura, Natsue Miyashita, Tomoyuki Tagawa, Kazuhiko Wada, Yo-ichi Enokido, Yasushi Marubuchi, Shigeki Harjes, Phoebe Arai, Nobutaka Oyanagi, Kiyomitsu Blandino, Giovanni Sudol, Marius Rich, Tina Kanazawa, Ichiro Wanker, Erich E. Saitoe, Minoru Okazawa, Hitoshi Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 |
title | Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 |
title_full | Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 |
title_fullStr | Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 |
title_full_unstemmed | Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 |
title_short | Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73 |
title_sort | transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of yap isoforms and p73 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063678/ https://www.ncbi.nlm.nih.gov/pubmed/16461361 http://dx.doi.org/10.1083/jcb.200509132 |
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