RRC ID |
34882
|
Author |
Wu C, Chen C, Dai J, Zhang F, Chen Y, Li W, Pastor-Pareja JC, Xue L.
|
Title |
Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila.
|
Journal |
Open Biol
|
Abstract |
Signalling networks that control the life or death of a cell are of central interest in modern biology. While the defined roles of the c-Jun N-terminal kinase (JNK) pathway in regulating cell death have been well-established, additional factors that modulate JNK-mediated cell death have yet to be fully elucidated. To identify novel regulators of JNK-dependent cell death, we performed a dominant-modifier screen in Drosophila and found that the Toll pathway participates in JNK-mediated cell death. Loss of Toll signalling suppresses ectopically and physiologically activated JNK signalling-induced cell death. Our epistasis analysis suggests that the Toll pathway acts as a downstream modulator for JNK-dependent cell death. In addition, gain of JNK signalling results in Toll pathway activation, revealed by stimulated transcription of Drosomycin (Drs) and increased cytoplasm-to-nucleus translocation of Dorsal. Furthermore, the Spätzle (Spz) family ligands for the Toll receptor are transcriptionally upregulated by activated JNK signalling in a non-cell-autonomous manner, providing a molecular mechanism for JNK-induced Toll pathway activation. Finally, gain of Toll signalling exacerbates JNK-mediated cell death and promotes cell death independent of caspases. Thus, we have identified another important function for the evolutionarily conserved Toll pathway, in addition to its well-studied roles in embryonic dorso-ventral patterning and innate immunity.
|
Volume |
5(7)
|
Pages |
140171
|
Published |
2015-7-1
|
DOI |
10.1098/rsob.140171
|
PII |
rsob.140171
|
PMID |
26202785
|
PMC |
PMC4632500
|
MeSH |
Animals
Cell Death / genetics
Compound Eye, Arthropod / cytology
Compound Eye, Arthropod / growth & development
Drosophila / cytology
Drosophila / metabolism*
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila Proteins / physiology
Forkhead Transcription Factors / metabolism
Gene Expression Regulation, Developmental
MAP Kinase Signaling System*
Signal Transduction
Toll-Like Receptors / metabolism*
Toll-Like Receptors / physiology
Wings, Animal / cytology
Wings, Animal / growth & development
|
IF |
4.931
|
Times Cited |
28
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Drosophila |
105520R-1
10520R-3
5576R-1
5576R-2
5848R-1
5848R-3
5680R-2 |