title: ALDOB acts as a novel HBsAg-binding protein and its coexistence inhibits cisplatin-induced HepG2 cell apoptosis.
abstract: Chronic infection with hepatitis B virus is a cause of end-stage liver disease and hepatocellular carcinoma (HCC). We previously screened fructose-bisphosphate aldolase B (ALDOB) as a candidate binding protein of hepatitis B surface antigen (HBsAg) using a yeast 2-hybrid assay. In this study we aimed to confirm ALDOB as a binding protein of the S region of the HbsAg (HBs) and to investigate the function and involved mechanism between its interactions during HCC development. Our results demonstrated that both of exogenous and endogenous ALDOB proteins bind to HBs and colocalize in the cytoplasm in vitro. The coexistence of HBs and ALDOB inhibit apoptosis of cisplatin-induced HepG2 cells. Furthermore, western blot analysis showed the coexistence of HBs and ALDOB enhance the phosphorylations of AKT and its downstream of GSK-3β (phosphorylation); decreased expression of the pro-apoptotic proteins Bax, Bid, Bim, and Puma; and increased expression of the prosurvival proteins Bcl-2, Bcl-xl, and Mcl-1 in HepG2 cells. These findings suggest that interaction between HBs and ALDOB might be applied as a potential therapeutic target during the treatment of HBV-related hepatitis or HCC.
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors: Jing
authors: J
authors: Wu
authors: Medical College of Xiamen University, Xiamen, Fujian Province, China, 361005.
authors: Can
authors: C
authors: Dan
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors: Hong-Bo
authors: HB
authors: Zhao
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors: Chuan-Xing
authors: CX
authors: Xiao
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors: Yun-Peng
authors: YP
authors: Liu
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors: Li-Juan
authors: LJ
authors: Si
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China.
authors: Jian-Lin
authors: JL
authors: Ren
authors: Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, China; Medical College of Xiamen University, Xiamen, Fujian Province, China, 361005.
authors: Bayasi
authors: B
authors: Guleng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000096:biosynthesis; D000072224:Bcl-2-Like Protein 11; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000378:metabolism*; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology; D008565:Membrane Proteins / Q000096:biosynthesis; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C494811:BCL2L1 protein, human; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D000072224:Bcl-2-Like Protein 11; D006514:Hepatitis B Surface Antigens; C579095:MCL1 protein, human; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005634:Fructose-Bisphosphate Aldolase; D002945:Cisplatin