Nature Communications (Aug 2020)

ABL1-dependent OTULIN phosphorylation promotes genotoxic Wnt/β-catenin activation to enhance drug resistance in breast cancers

  • Wei Wang,
  • Mingqi Li,
  • Suriyan Ponnusamy,
  • Yayun Chi,
  • Jingyan Xue,
  • Beshoy Fahmy,
  • Meiyun Fan,
  • Gustavo A. Miranda-Carboni,
  • Ramesh Narayanan,
  • Jiong Wu,
  • Zhao-Hui Wu

DOI
https://doi.org/10.1038/s41467-020-17770-9
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 15

Abstract

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Genotoxic agents have been shown to activate the Wnt/β-catenin signaling but the underlying mechanism remains unclear. Here, the authors show that upon DNA damage, the deubiquitinase OTULIN activates Wnt/β-catenin signaling by inhibiting linear ubiquitination, K48-linked polyubiquitination, and proteasomal degradation of β-catenin.