title: Bag-1L is a stress-withstand molecule prevents the downregulation of Mcl-1 and c-Raf under control of heat shock proteins in cisplatin treated HeLa cervix cancer cells.
abstract: Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy. Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motility and also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatin- induced apoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time- and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, 10 μM Cisplatin treatment induced cell death within 24h by activating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.
authors: Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istanbul Kultur University, Atakoy, Turkey E-mail : d.arisan@iku.edu.tr.
authors: Pelin
authors: P
authors: Ozfiliz
authors: Elif Damla
authors: ED
authors: Arisan
authors: Ajda
authors: A
authors: Coker-Gurkan
authors: Pinar
authors: P
authors: Obakan
authors: Tugce Nur
authors: TN
authors: Eralp
authors: Gizem
authors: G
authors: Dinler-Doganay
authors: Narcin
authors: N
authors: Palavan-Unsal
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D019908:Proto-Oncogene Proteins c-raf; D002945:Cisplatin