title: GABAA receptor-binding protein promotes sensitivity to apoptosis induced by chemotherapeutic agents.
abstract: In the present study, the expression of human γ-aminobutyrate type A (GABAA) receptor-binding protein (GABARBP) is downregulated in ovarian cancer cell lines and tissues. We also found that the specific function of GABAPBP was that of a novel pro-apoptotic protein. Both GABARBP and cisplatin suppressed cancer cell proliferation in a concentration-dependent manner. The combined treatment of GABARBP and cisplatin was more effective in inhibiting cell growth, as well as cell migration, than with either drug treatment alone. At the same time, the treatment combination is correlated with the downregulation of cyclin D1 and CDK4, arrested cell cycle progression in the G₀-G₁ phase and enhancing p53 expression, while also reducing Bcl-2 and Bcl-xL expression. The p53 and p21 promoter luciferase activities were induced by GABARBP, whereas there was no effect on the p53-/- and p21-/- system. In addition, p53 activity was validated with UV irradiation and siGABARBP. Taken together, our results indicate that GABARBP can regulate the pro-apoptotic activity of cisplatin via the upregulation of p53 expression.
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea. sbrho@ncc.re.kr
authors.forename: Seung Bae
authors.initials: SB
authors.lastname: Rho
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Byun
authors.forename: Boh-Ram
authors.initials: BR
authors.lastname: Kim
authors.forename: Ik Sun
authors.initials: IS
authors.lastname: Kim
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Yoo
authors.forename: Sung Taek
authors.initials: ST
authors.lastname: Park
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C530104:CCND1 protein, human; C116741:GABARAP protein, human; D008869:Microtubule-Associated Proteins; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D002945:Cisplatin