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Oncogenic AKTivation by methylation

Nature Cell Biology volume 21, pages 114–115 (2019)Cite this article

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AKT, also known as protein kinase B, is one of the most frequently dysregulated serine/threonine kinases in cancer, and its hyperactivity drives tumorigenesis and chemotherapy resistance. Two studies now find that AKT methylation by the methyltransferase SETDB1 is an early step in its oncogenic activation.

The AKT kinase is one of the most important intracellular signalling hubs for integrating diverse extracellular signals into control of cell proliferation, survival and metabolism. Dysregulated AKT signalling is associated with many human diseases, including cancer, in which AKT hyperactivity is a major biomarker of tumour severity. Intense ongoing efforts have uncovered a myriad of AKT post-translational modifications (PTMs) that influence its activity, with two activating phosphorylation events by the PDK1 and mTOR kinases being the most prominent. However, other PTMs besides phosphorylation continue to prove important for AKT regulation1,2. In this issue of Nature Cell Biology, two independent studies uncover methylation by the SETDB1 methyltransferase as a key early step in AKT activation3,4 and as an oncogenic marker in certain cancers.

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Fig. 1: Methylation stimulates AKT activation.

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Authors and Affiliations

  1. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Amelia K. Luciano & David A. Guertin

  2. Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA

    David A. Guertin

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  1. Amelia K. Luciano
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  2. David A. Guertin
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Correspondence to David A. Guertin.

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The authors declare no competing interests.

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Luciano, A.K., Guertin, D.A. Oncogenic AKTivation by methylation. Nat Cell Biol 21, 114–115 (2019). https://doi.org/10.1038/s41556-019-0275-8

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