The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis

Cancer Cell. 2008 Apr;13(4):343-54. doi: 10.1016/j.ccr.2008.02.001.


The balance between cell death and survival, two critical aspects of oncogenic transformation, determines the outcome of tumorigenesis. Nuclear factor-kappaB (NF-kappaB) is a critical regulator of survival; it is induced by the oncogene Ras and, when inhibited, accounts for the cell death response of Ras-transformed cells. Here, we show that the signaling adaptor p62 is induced by Ras, its levels are increased in human tumors, and it is required for Ras-induced survival and transformation. p62-/- mice are resistant to Ras-induced lung adenocarcinomas. p62 is necessary for Ras to trigger IkappaB kinase (IKK) through the polyubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), and its deficiency produces increased reactive oxygen species (ROS) levels, which account for the enhanced cell death and reduced tumorigenicity of Ras in the absence of p62.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Cell Transformation, Neoplastic*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • NF-kappa B / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • RNA-Binding Proteins / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Transcription, Genetic
  • ras Proteins / metabolism


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • KHDRBS1 protein, human
  • Khdrbs1 protein, mouse
  • NF-kappa B
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • ras Proteins