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

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Item Type:Article
Title:Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73
Creators Name:Hoshino, M. and Qi, M.L. and Yoshimura, N. and Miyashita, T. and Tagawa, K. and Wada, Y.I. and Enokido, Y. and Marubuchi, S. and Arai, P. and Arai, N. and Oyanagi, K. and Blandino, G. and Sudol, M. and Rich, T. and Kanazawa, I. and Wanker, E.E. and Saitoe, M. and Okazawa, H.
Abstract: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 (YAPDeltaCs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAPDeltaCs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAPDeltaCs 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.
Keywords:Signal Transducing Adaptor Proteins, Amanitins, Amino Acid Sequence, Apoptosis Regulatory Proteins, Cell Death, Cell Survival, Cultured Cells,, DNA-Binding Proteins, Animal Disease Models, Down-Regulation, Drosophila melanogaster, Embryo Research, Tumor Suppressor Genes, Huntington Disease, Molecular Sequence Data, Insertional Mutagenesis, Neurons, Nuclear Proteins, Phosphoproteins, Protein Isoforms, Small Interfering RNA, Time Factors, Trans-Activators, Genetic Transcription, Tumor Suppressor Proteins, Animals, Mice, Rats
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:172
Number:4
Page Range:589-604
Date:13 February 2006
Additional Information:Copyright (c) 2006 by Rockefeller University Press
Official Publication:https://doi.org/10.1083/jcb.200509132
PubMed:View item in PubMed

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