RRC ID 34888
著者 Wu C, Chen Y, Wang F, Chen C, Zhang S, Li C, Li W, Wu S, Xue L.
タイトル Pelle Modulates dFoxO-Mediated Cell Death in Drosophila.
ジャーナル PLoS Genet
Abstract Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis.
巻・号 11(10)
ページ e1005589
公開日 2015-10-1
DOI 10.1371/journal.pgen.1005589
PII PGENETICS-D-14-03320
PMID 26474173
PMC PMC4608839
MeSH Animals Apoptosis / genetics* Carcinogenesis / genetics Drosophila / genetics Drosophila Proteins / genetics* Drosophila Proteins / metabolism Forkhead Transcription Factors / genetics* Forkhead Transcription Factors / metabolism Humans Immunity, Innate / genetics* Interleukin-1 Receptor-Associated Kinases / genetics Phosphorylation Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Signal Transduction / genetics Wings, Animal / growth & development Wings, Animal / metabolism
IF 5.175
引用数 10
WOS 分野 GENETICS & HEREDITY
リソース情報
ショウジョウバエ 10520R-1 10520R-3 6667R-2 6667R-5 5848R-3 4006R-1