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

被引:77
作者
Hoshino, M
Qi, ML
Yoshimura, N
Miyashita, T
Tagawa, K
Wada, Y
Enokido, Y
Marubuchi, S
Harjes, P
Arai, N
Oyanagi, K
Blandino, G
Sudol, M
Rich, T
Kanazawa, I
Wanker, EE
Saitoe, M
Okazawa, H [1 ]
机构
[1] Tokyo Med & Dent Univ, Dept Neuropathol, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan
[2] Tokyo Med & Dent Univ, Bunkyo Ku, Ctr Excellence Program Brain Integrat & Its Disor, Tokyo 1138510, Japan
[3] Tokyo Metropolitan Inst Neurosci, Fuchu, Tokyo 1838526, Japan
[4] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany
[5] Regina Elena Inst Canc Res, Dept Expt Oncol, I-00158 Rome, Italy
[6] Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA
[7] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[8] Natl Ctr Neurol & Psychiat, Kodaira, Tokyo 1878502, Japan
[9] Japan Sci & Technol Agcy, Kawagoe, Saitama 3320012, Japan
关键词
D O I
10.1083/jcb.200509132
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 pro. ling 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 (YAP Delta Cs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAP Delta Cs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAP Delta Cs 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.
引用
收藏
页码:589 / 604
页数:16
相关论文
共 48 条
  • [21] Ataxin-1 nuclear localization and aggregation:: Role in polyglutamine-induced disease in SCA1 transgenic mice
    Klement, IA
    Skinner, PJ
    Kaytor, MD
    Yi, H
    Hersch, SM
    Clark, HB
    Zoghbi, HY
    Orr, HT
    [J]. CELL, 1998, 95 (01) : 41 - 53
  • [22] Cell biology - Autophagy as a regulated pathway of cellular degradation
    Klionsky, DJ
    Emr, SD
    [J]. SCIENCE, 2000, 290 (5497) : 1717 - 1721
  • [23] Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation
    Kouroku, Y
    Fujita, E
    Jimbo, A
    Kikuchi, T
    Yamagata, T
    Momoi, MY
    Kominami, E
    Kuida, K
    Sakamaki, K
    Yonehara, S
    Momoi, T
    [J]. HUMAN MOLECULAR GENETICS, 2002, 11 (13) : 1505 - 1515
  • [24] p73 induces apoptosis via PUMA transactivation and Bax mitochondrial translocation
    Melino, G
    Bernassola, F
    Ranalli, M
    Yee, K
    Zong, WX
    Corazzari, M
    Knight, RA
    Green, DR
    Thompson, C
    Vousden, KH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (09) : 8076 - 8083
  • [25] p53 has a direct apoptogenic role at the mitochondria
    Mihara, M
    Erster, S
    Zaika, A
    Petrenko, O
    Chittenden, T
    Pancoska, P
    Moll, UM
    [J]. MOLECULAR CELL, 2003, 11 (03) : 577 - 590
  • [26] Autophagosome-like vacuole formation in Huntington's disease lymphoblasts
    Nagata, E
    Sawa, A
    Ross, CA
    Snyder, SH
    [J]. NEUROREPORT, 2004, 15 (08) : 1325 - 1328
  • [27] Coordination of transcription, RNA processing, and surveillance by P-TEFb kinase on heat shock genes
    Ni, ZY
    Schwartz, BE
    Werner, J
    Suarez, JR
    Lis, JT
    [J]. MOLECULAR CELL, 2004, 13 (01) : 55 - 65
  • [28] ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats
    Nishitoh, H
    Matsuzawa, A
    Tobiume, K
    Saegusa, K
    Takeda, K
    Inoue, K
    Hori, S
    Kakizuka, A
    Ichijo, H
    [J]. GENES & DEVELOPMENT, 2002, 16 (11) : 1345 - 1355
  • [29] Polyglutamine diseases: a transcription disorder?
    Okazawa, H
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2003, 60 (07) : 1427 - 1439
  • [30] Interaction between mutant ataxin-1 and POBP-1 affects transcription and cell death
    Okazawa, H
    Rich, T
    Chang, A
    Lin, X
    Waragai, M
    Kajikawa, M
    Enokido, Y
    Komuro, A
    Kato, S
    Shibata, M
    Hatanaka, H
    Mouradian, MM
    Sudol, M
    Kanazawa, I
    [J]. NEURON, 2002, 34 (05) : 701 - 713