2014
DOI: 10.15252/embj.201488713
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SIRT 2 controls the pentose phosphate switch

Abstract: The most common enzyme defect in humans is glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, which affects more than 400 million people. G6PD shunts glucose into the pentose phosphate pathway (PPP) to generate nucleotides and reducing potential in the form of NADPH. In this issue, Wang et al () show that G6PD activity is post‐translationally regulated by SIRT2, a cytoplasmic NAD+‐dependent deacetylase, thereby linking NAD+ levels to DNA repair and oxidative defences, and identifying potential new approaches… Show more

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Cited by 16 publications
(16 citation statements)
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“…Post-translationally, G6PD is modified by lysine acetylation, phosphorylation, ubiquitination and O-GlcNAcylation 34 35 36 37 . We previously found that G6PD is deacetylated and activated by SIRT2 38 , which led us to explore the possibility of targeting SIRT2 to suppress G6PD and leukaemia 39 40 41 . SIRT2-mediated deacetylation of G6PD sustained NADPH production and promoted cell proliferation across different subtypes of AML.…”
Section: Discussionmentioning
confidence: 99%
“…Post-translationally, G6PD is modified by lysine acetylation, phosphorylation, ubiquitination and O-GlcNAcylation 34 35 36 37 . We previously found that G6PD is deacetylated and activated by SIRT2 38 , which led us to explore the possibility of targeting SIRT2 to suppress G6PD and leukaemia 39 40 41 . SIRT2-mediated deacetylation of G6PD sustained NADPH production and promoted cell proliferation across different subtypes of AML.…”
Section: Discussionmentioning
confidence: 99%
“…The rate-limiting step of the salvage pathway is catalyzed by NAMPT and requires PRPP as a cosubstrate, which is mostly supplied by the PPP pathway in cancer cells. 3 , 190 192 NAMPT was originally called pre-B-cell colony-enhancing factor (PBEF), a cytokine secreted by early B cells to promote maturation and proliferation. The NAMPT structure presents intracellular and extracellular forms (referred to as iNAMPT and eNAMPT, respectively).…”
Section: Nampt In Cancermentioning
confidence: 99%
“…Furthermore, in the pentose phosphate pathway (PPP), glucose-6-phosphate (G6P) dehydrogenase (G6PD) converts G6P to 6-p-gluconate, when the NAD + -dependent SIRT2 deacetylates and activates G6PD. The PPP pathway converts NADP + to NADPH and regenerates the antioxidant glutathione (GSH), thus promoting cell survival during oxidative stress (Wu and Sinclair, 2014). A schematic representation of the subcellular NAD + balance is shown in Figure 2.…”
mentioning
confidence: 99%