title: HSP27 modulates survival signaling networks in cells treated with curcumin and TRAIL.
abstract: The combination of curcumin and TRAIL and their role in enhancing apoptotic cell death has been reported by many studies. However, the exact molecular mechanism of apoptosis mediated by curcumin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is not yet completely understood. In this study, we observed a close connection between dephosphorylated Akt and an increase in phosphorylated heat shock protein 27 (HSP27) during combined treatment with curcumin and TRAIL. Akt dephosphorylation was cumulatively regulated by protein phosphatase 1 (PP1), phosphoinositide-dependent kinase-1 (PDK1), and src. PP1 and PDK1 directly interacted with HSP27, whereas src indirectly interacted with HSP27 via the tumor necrosis factor receptor-associated factor 6 complex. In conclusion, HSP27 modulated cell survival by its interactions with various binding partners, depending on the level of phosphorylated HSP27.
authors.affiliation: Institute for Cancer Research, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jina
authors.initials: J
authors.lastname: Kim
authors.forename: So Y
authors.initials: SY
authors.lastname: Kim
authors.forename: Sujin
authors.initials: S
authors.lastname: Kang
authors.forename: Hyo R
authors.initials: HR
authors.lastname: Yoon
authors.forename: Bo K
authors.initials: BK
authors.lastname: Sun
authors.forename: Dongxu
authors.initials: D
authors.lastname: Kang
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Song
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; D017476:Receptors, Neuropeptide Y; D048029:TNF Receptor-Associated Factor 6; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C109491:neuropeptide Y4 receptor; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D003474:Curcumin