title: BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas.
abstract: Bcl-2 associated athanogene 3 (BAG3) contains multiple protein-binding motifs to mediate potential interactions with chaperons and/or other proteins, which is possibly ascribed to the multifaceted functions assigned to BAG3. The current study demonstrated that BAG3 directly interacted with glucose 6 phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). BAG3 suppressed the PPP flux, de novo DNA synthesis and cell growth in hepatocellular carcinomas (HCCs). The growth defect of HCCs with forced BAG3 expression can be rescued by enforced G6PD expression. However, BAG3 elevation did not cause a reduction in cellular NADPH concentrations, another main product of G6PD. In addition, supplement of nucleosides alone was sufficient to recover the growth defect mediated by BAG3 elevation. Collectively, the current study established a tumor suppressor-like function of BAG3 via direct interaction with G6PD in HCCs at the cellular level.
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.|Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: De-Hui
authors.initials: DH
authors.lastname: Kong
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.
authors.forename: Si
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, The 1st Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Zhen-Xian
authors.initials: ZX
authors.lastname: Du
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.
authors.forename: Bao-Qin
authors.initials: BQ
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zong
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China.|Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Hua-Qin
authors.initials: HQ
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009249:NADP / Q000378:metabolism; D009705:Nucleosides / Q000494:pharmacology; D010427:Pentose Phosphate Pathway / Q000235:genetics; D011485:Protein Binding
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D009705:Nucleosides; D009249:NADP; D005954:Glucosephosphate Dehydrogenase
keywords: BAG3; G6PD; HCCs; pentose phosphate pathway