Tumor Suppressor CYLD Regulates JNK-Induced Cell Death in Drosophila

Lei Xue, Tatsushi Igaki, Erina Kuranaga, Hiroshi Kanda, Masayuki Miura, Tian Xu

研究成果: Article査読

86 被引用数 (Scopus)

抄録

CYLD encodes a tumor suppressor that is mutated in familial cylindromatosis. Despite biochemical and cell culture studies, the physiological functions of CYLD in animal development and tumorigenesis remain poorly understood. To address these questions, we generated Drosophila CYLD (dCYLD) mutant and transgenic flies expressing wild-type and mutant dCYLD proteins. Here we show that dCYLD is essential for JNK-dependent oxidative stress resistance and normal lifespan. Furthermore, dCYLD regulates TNF-induced JNK activation and cell death through dTRAF2, which acts downstream of the TNF receptor Wengen and upstream of the JNKK kinase dTAK1. We show that dCYLD encodes a deubiquitinating enzyme that deubiquitinates dTRAF2 and prevents dTRAF2 from ubiquitin-mediated proteolytic degradation. These data provide a molecular mechanism for the tumor suppressor function of this evolutionary conserved molecule by indicating that dCYLD plays a critical role in modulating TNF-JNK-mediated cell death.

本文言語English
ページ(範囲)446-454
ページ数9
ジャーナルDevelopmental Cell
13
3
DOI
出版ステータスPublished - 2007 9 4
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 発生生物学
  • 細胞生物学

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