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SUMOylation of AMPKα1 by PIAS4 specifically regulates mTORC1 signalling

Author

Listed:
  • Yan Yan

    (Research Programs Unit, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki)

  • Saara Ollila

    (Research Programs Unit, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki)

  • Iris P. L. Wong

    (Research Programs Unit, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki)

  • Tea Vallenius

    (Research Programs Unit, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki)

  • Jorma J. Palvimo

    (Institute of Biomedicine, University of Eastern Finland, Kuopio)

  • Kari Vaahtomeri

    (Research Programs Unit, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki)

  • Tomi P. Mäkelä

    (Research Programs Unit, Faculty of Medicine, University of Helsinki, Biomedicum Helsinki)

Abstract

AMP-activated protein kinase (AMPK) inhibits several anabolic pathways such as fatty acid and protein synthesis, and identification of AMPK substrate specificity would be useful to understand its role in particular cellular processes and develop strategies to modulate AMPK activity in a substrate-specific manner. Here we show that SUMOylation of AMPKα1 attenuates AMPK activation specifically towards mTORC1 signalling. SUMOylation is also important for rapid inactivation of AMPK, to allow prompt restoration of mTORC1 signalling. PIAS4 and its SUMO E3 ligase activity are specifically required for the AMPKα1 SUMOylation and the inhibition of AMPKα1 activity towards mTORC1 signalling. The activity of a SUMOylation-deficient AMPKα1 mutant is higher than the wild type towards mTORC1 signalling when reconstituted in AMPKα-deficient cells. PIAS4 depletion reduced growth of breast cancer cells, specifically when combined with direct AMPK activator A769662, suggesting that inhibiting AMPKα1 SUMOylation can be explored to modulate AMPK activation and thereby suppress cancer cell growth.

Suggested Citation

  • Yan Yan & Saara Ollila & Iris P. L. Wong & Tea Vallenius & Jorma J. Palvimo & Kari Vaahtomeri & Tomi P. Mäkelä, 2015. "SUMOylation of AMPKα1 by PIAS4 specifically regulates mTORC1 signalling," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9979
    DOI: 10.1038/ncomms9979
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