TY - JOUR
T1 - Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73
AU - Hoshino, Masataka
AU - Qi, Mei Ling
AU - Yoshimura, Natsue
AU - Miyashita, Tomoyuki
AU - Tagawa, Kazuhiko
AU - Wada, Yo Ichi
AU - Enokido, Yasushi
AU - Marubuchi, Shigeki
AU - Harjes, Phoebe
AU - Arai, Nobutaka
AU - Oyanagi, Kiyomitsu
AU - Blandino, Giovanni
AU - Sudol, Marius
AU - Rich, Tina
AU - Kanazawa, Ichiro
AU - Wanker, Erich E.
AU - Saitoe, Minoru
AU - Okazawa, Hitoshi
PY - 2006/2/13
Y1 - 2006/2/13
N2 - 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.
AB - 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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U2 - 10.1083/jcb.200509132
DO - 10.1083/jcb.200509132
M3 - Article
C2 - 16461361
AN - SCOPUS:32644436068
VL - 172
SP - 589
EP - 604
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 4
ER -