Originally published as Genetics Published Articles Ahead of Print on August 3, 2005.

Genetics, Vol. 171, 1683-1694, December 2005, Copyright © 2005
doi:10.1534/genetics.105.045534

A Genetic Screen Targeting the Tumor Necrosis Factor/Eiger Signaling Pathway: Identification of Drosophila TAB2 as a Functionally Conserved Component

Peter Geuking, Rajesh Narasimamurthy and Konrad Basler¹

Institut für Molekularbiologie, Universität Zürich, CH-8057 Zürich, Switzerland

¹ Corresponding author: Institut für Molekularbiologie, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
E-mail: basler{at}molbio.unizh.ch

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.

This article has been cited by other articles:

				G. W. Glenney and G. D. Wiens Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis J. Immunol., June 15, 2007; 178(12): 7955 - 7973. [Abstract] [Full Text] [PDF]

				S. Polaski, L. Whitney, B. W. Barker, and B. Stronach Genetic Analysis of Slipper/Mixed Lineage Kinase Reveals Requirements in Multiple Jun-N-Terminal Kinase-Dependent Morphogenetic Events During Drosophila Development Genetics, October 1, 2006; 174(2): 719 - 733. [Abstract] [Full Text] [PDF]

International Access Link

Online ISSN: 1943-2361  Print ISSN: 0016-6731
Copyright 2009 by the Genetics Society of America
phone: 412-268-1812   fax: 412-268-1813   email: genetics-gsa{at}andrew.cmu.edu