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The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis
Open accessAbstract
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.
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“ALS-associated mutations in TBK1, OPTN, SQSTM1, and VCP all affect autophagy as well as microglial function and innate immunity [192,205,206,441–443].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [442]
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Metadata
- Authors
- Duran, A., Linares, J. F., Galvez, A. S., Wikenheiser, K., Flores, J. M., Diaz-Meco, M. T., & Moscat, J.
- Affiliations
- University of Cincinnati (US)
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Moscat, Jorge
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 13
- Issue
- 4
- Pages
- 343-354
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1981912182
- Cited by
- 541
- References
- 51
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 13 · 2023: 18 · 2022: 30 · 2021: 35 · 2020: 41 · 2019: 39 · 2018: 41 · 2017: 51 · 2016: 41 · 2015: 38 · 2014: 41 · 2013: 45 · 2012: 29
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- Cincinnati Children's Hospital Medical Center
- University of Cincinnati
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- p62, NF-κB signaling, oncogenic Ras, carcinogenesis, cell survival, cell death, TRAF6, IκB kinase, polyubiquitination, reactive oxygen species, lung adenocarcinoma, oncogenic transformation
- MeSH terms
- Animals, Cell Survival, Cell Transformation, Neoplastic, DNA-Binding Proteins, Humans, Lung Neoplasms, Neoplasms, Transcription, Genetic, Signal Transduction, NF-kappa B, RNA-Binding Proteins, Reactive Oxygen Species, ras Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice
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