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Proteasome inhibitors suppress MYB oncogenic activity in a p300-dependent manner

Authors

  • M.V. Yusenko
  • A. Biyanee
  • M.K. Andersson
  • S. Radetzki
  • J.P. von Kries
  • G. Stenman
  • K.H. Klempnauer

Journal

  • Cancer Letters

Citation

  • Cancer Lett 520: 132-142

Abstract

  • Studies of the role of MYB in human malignancies have highlighted MYB as a potential drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC). Although transcription factors are often considered un-druggable, recent work has demonstrated successful targeting of MYB by low molecular weight compounds. This has fueled the notion that inhibition of MYB has potential as a therapeutic approach against MYB-driven malignancies. Here, we have used a MYB reporter cell line to screen a library of FDA-approved drugs for novel MYB inhibitors. We demonstrate that proteasome inhibitors have significant MYB-inhibitory activity, prompting us to characterize the proteasome inhibitor oprozomib in more detail. Oprozomib was shown to interfere with the ability of the co-activator p300 to stimulate MYB activity and to exert anti-proliferative effects on human AML and ACC cells. Overall, our work demonstrated suppression of oncogenic MYB activity as a novel result of proteasome inhibition.


DOI

doi:10.1016/j.canlet.2021.07.010