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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., Qi, M.L., Yoshimura, N., Miyashita, T., Tagawa, K., Wada, Y.I., Enokido, Y., Marubuchi, S., Arai, P., Arai, N., Oyanagi, K., Blandino, G., Sudol, M., Rich, T., Kanazawa, I., Wanker, E.E., 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 |
| 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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