Research ArticleCancer

Activating mutations in MEK1 enhance homodimerization and promote tumorigenesis

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Science Signaling  30 Oct 2018:
Vol. 11, Issue 554, eaar6795
DOI: 10.1126/scisignal.aar6795

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Know thine enemy: Mutant MEK

Many cancers, notably melanomas, are driven by activation of the RAS-ERK signaling pathway, but tumors are often resistant to pathway-targeted therapies. Yuan et al. characterized cancer-related mutations in the pathway-mediating kinase MEK1 and found that deletion mutations in a loop portion of the protein promoted MEK1 homodimerization and autophosphorylation, enabling the activation of ERK with or without upstream pathway activity. These mutants transformed cells and differentially conferred resistance to MEK inhibitors. Understanding the precise functions of these mutants and detecting them at diagnosis may help devise more effective treatment strategies for patients.