A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation. / de Vreede, Geert; Morrison, Holly A; Houser, Alexandra M; Boileau, Ryan M; Andersen, Ditte; Colombani, Julien; Bilder, David.
In: Developmental Cell, Vol. 45, No. 5, 04.06.2018, p. 595-605.e4.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A Drosophila Tumor Suppressor Gene Prevents Tonic TNF Signaling through Receptor N-Glycosylation
AU - de Vreede, Geert
AU - Morrison, Holly A
AU - Houser, Alexandra M
AU - Boileau, Ryan M
AU - Andersen, Ditte
AU - Colombani, Julien
AU - Bilder, David
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/6/4
Y1 - 2018/6/4
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Proliferation
KW - Drosophila Proteins/genetics
KW - Drosophila melanogaster/genetics
KW - Female
KW - Genes, Tumor Suppressor
KW - Glycosylation
KW - Imaginal Discs/growth & development
KW - Intracellular Signaling Peptides and Proteins/genetics
KW - JNK Mitogen-Activated Protein Kinases/genetics
KW - Male
KW - Mutation
KW - Phenotype
KW - Protein-Serine-Threonine Kinases/genetics
KW - Receptors, Tumor Necrosis Factor/genetics
KW - Signal Transduction
U2 - 10.1016/j.devcel.2018.05.012
DO - 10.1016/j.devcel.2018.05.012
M3 - Journal article
C2 - 29870719
VL - 45
SP - 595-605.e4
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 5
ER -
ID: 212682643