Tumor Suppressor CYLD Regulates JNK-Induced Cell Death in Drosophila

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

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)446-454
Number of pages9
JournalDevelopmental Cell
Volume13
Issue number3
DOIs
Publication statusPublished - 2007 Sep 4
Externally publishedYes

Fingerprint

Cell death
Drosophila
Tumors
Cell Death
Oxidative stress
Tumor Necrosis Factor Receptors
Ubiquitin
Cell culture
Neoplasms
Animals
Phosphotransferases
Chemical activation
Degradation
Molecules
Enzymes
Mutant Proteins
Diptera
Carcinogenesis
Oxidative Stress
Cell Culture Techniques

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Xue, L., Igaki, T., Kuranaga, E., Kanda, H., Miura, M., & Xu, T. (2007). Tumor Suppressor CYLD Regulates JNK-Induced Cell Death in Drosophila. Developmental Cell, 13(3), 446-454. https://doi.org/10.1016/j.devcel.2007.07.012

Tumor Suppressor CYLD Regulates JNK-Induced Cell Death in Drosophila. / Xue, Lei; Igaki, Tatsushi; Kuranaga, Erina; Kanda, Hiroshi; Miura, Masayuki; Xu, Tian.

In: Developmental Cell, Vol. 13, No. 3, 04.09.2007, p. 446-454.

Research output: Contribution to journalArticle

Xue, L, Igaki, T, Kuranaga, E, Kanda, H, Miura, M & Xu, T 2007, 'Tumor Suppressor CYLD Regulates JNK-Induced Cell Death in Drosophila', Developmental Cell, vol. 13, no. 3, pp. 446-454. https://doi.org/10.1016/j.devcel.2007.07.012
Xue, Lei ; Igaki, Tatsushi ; Kuranaga, Erina ; Kanda, Hiroshi ; Miura, Masayuki ; Xu, Tian. / Tumor Suppressor CYLD Regulates JNK-Induced Cell Death in Drosophila. In: Developmental Cell. 2007 ; Vol. 13, No. 3. pp. 446-454.
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