Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction.
Death associated protein 3 (DAP3) is known to be a highly conserved protein, and is responsible for regulating apoptosis induced by various stimuli. To understand the molecular mechanism of how DAP3 induces apoptosis, we performed yeast two-hybrid screening, and identified a novel DAP3-binding protein termed death ligand signal enhancer (DELE). In this report, we show that DELE actually binds to DAP3 in mammalian cells. We found that the cells stably expressing DELE are susceptible to apoptosis induction by the stimulation of TNF-α and TRAIL. In addition, knockdown of DELE expression rescued the HeLa cells from apoptosis induction by these stimuli. Moreover, activation of caspase-3, caspase-8 and caspase-9 induced by stimulation of TNF-α, anti-Fas or TRAIL was significantly inhibited by the knockdown of DELE expression. These results demonstrated the biological significance of DELE for apoptosis signal mediated by death receptors.
Harada
Tanenobu
T
Department of Bioresources, Hokkaido University Research Center for Zoonosis Control, North 20, West 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan.
Iwai
Atsushi
A
Miyazaki
Tadaaki
T
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053218:Receptors, Death Domain / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; C554526:DELE1 protein, human; D024101:Mitochondrial Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053218:Receptors, Death Domain; D012269:Ribosomal Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9