Eiger and its receptor, Wengen, comprise a TNF-like system in Drosophila

Autor: Joe Chapo, Nisha Rathore, Sunny Zachariah, Walid S. Maaty, Suwan K. Sinha, Sukit Chew, Preet M. Chaudhary, Michael T. Eby, Raghuvir S Tomar, Saila Kauppila, Po Chen, John M. Abrams
Rok vydání: 2003
Předmět:
Cancer Research
TRAF2
Programmed cell death
DNA
Complementary
Embryo
Nonmammalian
Glycosylation
MAP Kinase Kinase 4
Recombinant Fusion Proteins
Molecular Sequence Data
Apoptosis
Biology
Transfection
Receptors
Tumor Necrosis Factor
Evolution
Molecular
Species Specificity
Drosophilidae
Genetics
Phosphoprotein Phosphatases
Animals
Drosophila Proteins
RNA
Antisense
Amino Acid Sequence
Gene Silencing
RNA
Small Interfering
Molecular Biology
RNA
Double-Stranded
Regulation of gene expression
Mitogen-Activated Protein Kinase Kinases
Sequence Homology
Amino Acid
Tumor Necrosis Factor-alpha
JNK Mitogen-Activated Protein Kinases
Gene Expression Regulation
Developmental
Membrane Proteins
Proteins
biology.organism_classification
TNF Receptor-Associated Factor 2
Molecular biology
Cell biology
Cell killing
Drosophila melanogaster
Signal transduction
Protein Processing
Post-Translational
Sequence Alignment
Drosophila Protein
DNA Damage
Signal Transduction
Zdroj: Oncogene. 22(31)
ISSN: 0950-9232
Popis: In mammals, members of the tumor necrosis factor (TNF) family play an important role in the regulation of cellular proliferation, differentiation and programmed cell death. We describe isolation and characterization of an orthologous ligand/receptor axis in Drosophila. The ligand, designated Eiger, is a type II membrane glycosylated protein, which can be cleaved at residue 145 and released from the cell surface as a soluble factor, thereby representing the first potential cytokine to be described in Drosophila. Eiger exists in two alternatively spliced isoforms, Eiger long (Eiger-L) and Eiger short (Eiger-s), both of which are expressed throughout development and in the adult. We also describe the isolation and characterization of a novel Drosophila member of the TNF receptor family, designated Wengen, which is a type I membrane protein that can physically interact with the recently described TRAF2 homolog dTRAF2. Both Eiger and Wengen are expressed in distinctive patterns during embryogenesis and Eiger is responsive to genotoxic stress. Forced expression of Eiger-L, Eiger-s or Wengen, caused apoptotic cell death which could be rescued by caspase inhibitors or the JNK phosphatase Puckered. In addition, Eiger-induced cell killing was attenuated by RNAi-mediated suppression of Wengen. Our results illustrate that Eiger and Wengen represent proximal components of an evolutionarily conserved TNF-like signaling pathway in Drosophila.
Databáze: OpenAIRE
Externí odkaz: