A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation

Research output: Contribution to journalJournal articleResearchpeer-review

Drosophila tumor suppressor genes have revealed molecular pathways that control tissue growth, but mechanisms that regulate mitogenic signaling are far from understood. Here we report that the Drosophila TSG tumorous imaginal discs (tid), whose phenotypes were previously attributed to mutations in a DnaJ-like chaperone, are in fact driven by the loss of the N-linked glycosylation pathway component ALG3. tid/alg3 imaginal discs display tissue growth and architecture defects that share characteristics of both neoplastic and hyperplastic mutants. Tumorous growth is driven by inhibited Hippo signaling, induced by excess Jun N-terminal kinase (JNK) activity. We show that ectopic JNK activation is caused by aberrant glycosylation of a single protein, the fly tumor necrosis factor (TNF) receptor homolog, which results in increased binding to the continually circulating TNF. Our results suggest that N-linked glycosylation sets the threshold of TNF receptor signaling by modifying ligand-receptor interactions and that cells may alter this modification to respond appropriately to physiological cues.

Original languageEnglish
JournalDevelopmental Cell
Volume45
Issue number5
Pages (from-to)595-605.e4
ISSN1534-5807
DOIs
Publication statusPublished - 4 Jun 2018
Externally publishedYes

Bibliographical note

Copyright © 2018 Elsevier Inc. All rights reserved.

    Research areas

  • Animals, Cell Proliferation, Drosophila Proteins/genetics, Drosophila melanogaster/genetics, Female, Genes, Tumor Suppressor, Glycosylation, Imaginal Discs/growth & development, Intracellular Signaling Peptides and Proteins/genetics, JNK Mitogen-Activated Protein Kinases/genetics, Male, Mutation, Phenotype, Protein-Serine-Threonine Kinases/genetics, Receptors, Tumor Necrosis Factor/genetics, Signal Transduction

ID: 212682643