title: AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells.
abstract: BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer.
authors.affiliation: Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Ngai Na
authors.initials: NN
authors.lastname: Co
authors.forename: Wing Pui
authors.initials: WP
authors.lastname: Tsang
authors.forename: Tsun Yee
authors.initials: TY
authors.lastname: Tsang
authors.forename: Chi Lam Au
authors.initials: CL
authors.lastname: Yeung
authors.forename: Pak Lun
authors.initials: PL
authors.lastname: Yau
authors.forename: Siu Kai
authors.initials: SK
authors.lastname: Kong
authors.forename: Tim Tak
authors.initials: TT
authors.lastname: Kwok
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects*; D001483:Base Sequence; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C494819:BAD protein, human; D001798:Blood Proteins; C091736:MLLT11 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D051025:bcl-Associated Death Protein