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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-990

Geuking, Peter; Narasimamurthy, Rajesh; Basler, Konrad (2005). A genetic screen targeting the tumor necrosis factor/Eiger signaling pathway: identification of Drosophila TAB2 as a functionally conserved component. Genetics, 171(4):1683-1694.

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Abstract

Signaling by tumor necrosis factors (TNFs) plays a prominent role in mammalian development and disease. To fully understand this complex signaling pathway it is important to identify all regulators and transduction components. A single TNF family member, Eiger, is encoded in the Drosophila genome, offering the possibility of applying genetic approaches for pursuing this goal. Here we present a screen for the isolation of novel genes involved in the TNF/Eiger pathway. On the basis of Eiger's ability to potently activate Jun-N-terminal kinase (JNK) and trigger apoptosis, we used the Drosophila eye to establish an assay for dominant suppressors of this activity. In a large-scale screen the Drosophila homolog of TAB2/3 (dTAB2) was identified as an essential component of the Eiger-JNK pathway. Genetic epistasis and biochemical protein-protein interaction assays assign an adaptor role to dTAB2, linking dTRAF1 to the JNKKK dTAK1, demonstrating a conserved mechanism of TNF signal transduction in mammals and Drosophila. Thus, in contrast to morphogenetic processes, such as dorsal closure of the embryo, in which the JNK pathway is activated by the JNKKK Slipper, Eiger uses the dTAB2-dTAK1 module to induce JNK signaling activity.

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
DDC:570 Life sciences; biology
Language:English
Date:December 2005
Deposited On:11 Feb 2008 12:19
Last Modified:14 Dec 2013 05:26
Publisher:Genetics Society of America
ISSN:0016-6731
Publisher DOI:10.1534/genetics.105.045534
Related URLs:http://www.genetics.org/
PubMed ID:16079232
Citations:Web of Science®. Times Cited: 30
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