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SUMOylation regulates AKT1 activity

Oncogene volume 34, pages 1442–1450 (2015)Cite this article

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Abstract

Serine threonine kinase AKT has a central role in the cell, controlling survival, proliferation, metabolism and angiogenesis. Deregulation of its activity underlies a wide range of pathological situations, including cancer. Here we show that AKT is post-translationally modified by the small ubiquitin-like modifier (SUMO) protein. Interestingly, neither SUMO conjugation nor activation of SUMOylated AKT is regulated by the classical AKT targeting to the cell membrane or by the phosphoinositide 3-kinase pathway. We demonstrate that SUMO induces the activation of AKT, whereas, conversely, down-modulation of the SUMO machinery diminishes AKT activation and cell proliferation. Furthermore, an AKT SUMOylation mutant shows reduced activation, and decreased anti-apoptotic and pro-tumoral activities in comparison with the wild-type protein. These results identify SUMO as a novel key regulator of AKT phosphorylation and activity.

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Acknowledgements

We thank Dr William R Sellers who deposited AKT plamids at Addgene. Funding at the laboratory of CR is provided by BFU-2011–27064. LM-V is supported by Juan de la Cierva Programme. CFC-H is supported by La Caixa fellowship. MC is an investigator of the Miguel Servet Program.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Madrid, Spain

    C F de la Cruz-Herrera, M Campagna, J del Carmen González-Santamaría, L Marcos-Villar & C Rivas

  2. Ubiquitylation and Cancer Molecular Biology laboratory, Inbiomed, San Sebastian-Donostia, Gipuzkoa, Spain

    V Lang & M S Rodríguez

  3. Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain

    A Vidal

  4. Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Santiago de Compostela, Spain

    M Collado

  5. Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain

    C Rivas

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  1. C F de la Cruz-Herrera
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Correspondence to C Rivas.

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de la Cruz-Herrera, C., Campagna, M., Lang, V. et al. SUMOylation regulates AKT1 activity. Oncogene 34, 1442–1450 (2015). https://doi.org/10.1038/onc.2014.48

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