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Acetylation of MAT IIα represses tumour cell growth and is decreased in human hepatocellular cancer

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  • Hong-Bin Yang

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University)

  • Ying-Ying Xu

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University)

  • Xiang-Ning Zhao

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University
    Shanghai 10th People’s Hospital, Tong Ji University)

  • Shao-Wu Zou

    (Shanghai 10th People’s Hospital, Tong Ji University)

  • Ye Zhang

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University)

  • Min Zhang

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University)

  • Jin-Tao Li

    (Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University)

  • Feng Ren

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University)

  • Li-Ying Wang

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University)

  • Qun-Ying Lei

    (Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University
    Cancer Metabolism Lab, Institutes of Biomedical Sciences, Fudan University
    Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiaotong University)

Abstract

Metabolic alteration is a hallmark of cancer. Dysregulation of methionine metabolism is implicated in human liver cancer. Methionine adenosyltransferase IIα (MAT IIα) is a key enzyme in the methionine cycle, catalysing the production of S-adenosylmethionine (SAM), a key methyl donor in cellular processes, and is associated with uncontrolled cell proliferation in cancer. Here we show that P300 acetylates MAT IIα at lysine residue 81 and destabilizes MAT IIα by promoting its ubiquitylation and subsequent proteasomal degradation. Conversely, histone deacetylase-3 deacetylates and stabilizes MAT IIα by preventing its proteasomal degradation. Folate deprivation upregulates K81 acetylation and destabilizes MAT IIα to moderate cell proliferation, whereas a single mutation at K81 reverses the proliferative disadvantage of cancer cells upon folate deprivation. Moreover, MAT IIα K81 acetylation is decreased in human hepatocellular cancer. Collectively, our study reveals a novel mechanism of MAT IIα regulation by acetylation and ubiquitylation, and a direct functional link of this regulation to cancer development.

Suggested Citation

  • Hong-Bin Yang & Ying-Ying Xu & Xiang-Ning Zhao & Shao-Wu Zou & Ye Zhang & Min Zhang & Jin-Tao Li & Feng Ren & Li-Ying Wang & Qun-Ying Lei, 2015. "Acetylation of MAT IIα represses tumour cell growth and is decreased in human hepatocellular cancer," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7973
    DOI: 10.1038/ncomms7973
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    Cited by:

    1. Shiwen Wang & Bowen Jiang & Tengfei Zhang & Lixia Liu & Yi Wang & Yiping Wang & Xiufei Chen & Huaipeng Lin & Lisha Zhou & Yukun Xia & Leilei Chen & Chen Yang & Yue Xiong & Dan Ye & Kun-Liang Guan, 2015. "Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1," PLOS Biology, Public Library of Science, vol. 13(9), pages 1-27, September.

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