BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas.
BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas.
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BAG3 升高通过与肝细胞癌中的 G6PD 直接相互作用抑制细胞增殖
DOI：
10.18632/oncotarget.6396
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发表时间：
2016-01-05
期刊：
影响因子：
--
通讯作者：
Wang HQ
中科院分区：
文献类型：
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作者：
Kong DH;Li S;Du ZX;Liu C;Liu BQ;Li C;Zong ZH;Wang HQ
Bcl-2相关凋亡基因3（BAG 3）含有多个蛋白结合基序，可介导与分子伴侣和/或其他蛋白的潜在相互作用，这可能归因于BAG 3的多方面功能。目前的研究表明，BAG 3直接与葡萄糖6磷酸脱氢酶（G6 PD），戊糖磷酸途径（PPP）的限速酶相互作用。BAG 3抑制PPP流量，从头DNA合成和细胞生长在肝细胞癌（HCC）。通过加强G6 PD表达，可以挽救具有强制BAG 3表达的HCC的生长缺陷。然而，BAG 3升高并不引起细胞NADPH浓度的降低，这是G6 PD的另一种主要产物。此外，单独补充核苷足以恢复由BAG 3升高介导的生长缺陷。总的来说，本研究通过在细胞水平上与HCC中的G6 PD直接相互作用建立了BAG 3的肿瘤抑制剂样功能。
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.