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.