Oncotarget

Research Papers:

BAG3 elevation inhibits cell proliferation via direct interaction with G6PD in hepatocellular carcinomas

De-Hui Kong, Si Li, Zhen-Xian Du, Chuan Liu, Bao-Qin Liu, Chao Li, Zhi-Hong Zong and Hua-Qin Wang _

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Oncotarget. 2016; 7:700-711. https://doi.org/10.18632/oncotarget.6396

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Abstract

De-Hui Kong1,2, Si Li1, Zhen-Xian Du3, Chuan Liu4, Bao-Qin Liu1, Chao Li1, Zhi-Hong Zong1, Hua-Qin Wang1,2

1Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, China

2Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China

3Department of Endocrinology and Metabolism, The 1st Affiliated Hospital, China Medical University, Shenyang, China

4Department of Gynecology and Obstetrics, Shengjing Hospital, China Medical University, Shenyang, China

Correspondence to:

Hua-Qin Wang, e-mail: [email protected]

Keywords: BAG3, HCCs, G6PD, pentose phosphate pathway

Received: April 26, 2015     Accepted: November 14, 2015     Published: November 26, 2015

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.


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