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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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