Cancer Cell
Volume 13, Issue 4, 8 April 2008, Pages 343-354
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Article
The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis

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Summary

The balance between cell death and survival, two critical aspects of oncogenic transformation, determines the outcome of tumorigenesis. Nuclear factor-κB (NF-κB) 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 IκB 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.

CELLCYCLE
SIGNALING

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