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

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

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1
Department of Molecular Oncogenesis, Genome Research Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.

Abstract

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.

PMID:
18394557
DOI:
10.1016/j.ccr.2008.02.001
[Indexed for MEDLINE]
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