IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9468.html
   My bibliography  Save this article

O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth

Author

Listed:
  • Xiongjian Rao

    (Institute of Biochemistry, College of Life Sciences, Zhejiang University
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases)

  • Xiaotao Duan

    (State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology)

  • Weimin Mao

    (Zhejiang Cancer Hospital, Zhejiang Cancer Research Institute)

  • Xuexia Li

    (Institute of Biochemistry, College of Life Sciences, Zhejiang University)

  • Zhonghua Li

    (Institute of Biochemistry, College of Life Sciences, Zhejiang University
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases)

  • Qian Li

    (Institute of Biochemistry, College of Life Sciences, Zhejiang University)

  • Zhiguo Zheng

    (Zhejiang Cancer Hospital, Zhejiang Cancer Research Institute)

  • Haimiao Xu

    (Zhejiang Cancer Hospital, Zhejiang Cancer Research Institute)

  • Min Chen

    (School of Life Science and the State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University)

  • Peng G. Wang

    (School of Life Science and the State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University
    Georgia State University)

  • Yingjie Wang

    (Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases
    State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Zhejiang University)

  • Binghui Shen

    (City of Hope National Medical Center)

  • Wen Yi

    (Institute of Biochemistry, College of Life Sciences, Zhejiang University
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases)

Abstract

The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. Importantly, G6PD glycosylation is increased in human lung cancers. Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours.

Suggested Citation

  • Xiongjian Rao & Xiaotao Duan & Weimin Mao & Xuexia Li & Zhonghua Li & Qian Li & Zhiguo Zheng & Haimiao Xu & Min Chen & Peng G. Wang & Yingjie Wang & Binghui Shen & Wen Yi, 2015. "O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9468
    DOI: 10.1038/ncomms9468
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9468
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9468?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Leandro R. Soria & Georgios Makris & Alfonso M. D’Alessio & Angela Angelis & Iolanda Boffa & Veronica M. Pravata & Véronique Rüfenacht & Sergio Attanasio & Edoardo Nusco & Paola Arena & Andrew T. Fere, 2022. "O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Fang Wu & Natali H. Muskat & Inbar Dvilansky & Omri Koren & Anat Shahar & Roi Gazit & Natalie Elia & Eyal Arbely, 2023. "Acetylation-dependent coupling between G6PD activity and apoptotic signaling," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Yu-Lan Ma & Chun-Yan Kong & Zhen Guo & Ming-Yu Wang & Pan Wang & Fang-Yuan Liu & Dan Yang & Zheng Yang & Qi-Zhu Tang, 2024. "Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9468. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.