RRC ID 34882
著者 Wu C, Chen C, Dai J, Zhang F, Chen Y, Li W, Pastor-Pareja JC, Xue L.
タイトル Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila.
ジャーナル 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.
巻・号 5(7)
ページ 140171
公開日 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
引用数 28
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ショウジョウバエ 105520R-1 10520R-3 5576R-1 5576R-2 5848R-1 5848R-3 5680R-2