| Title | The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. |
| Publication Type | Journal Article |
| Year of Publication | 2008 |
| Authors | Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, Moscat J |
| Journal | Cancer Cell |
| Volume | 13 |
| Issue | 4 |
| Pagination | 343-54 |
| Date Published | 2008 Apr |
| ISSN | 1878-3686 |
| Keywords | Adaptor Proteins, Signal Transducing, Animals, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic, DNA-Binding Proteins, Humans, Lung Neoplasms, Mice, Neoplasms, NF-kappa B, ras Proteins, Reactive Oxygen Species, RNA-Binding Proteins, Signal Transduction, Transcription, Genetic |
| 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. |
| DOI | 10.1016/j.ccr.2008.02.001 |
| Alternate Journal | Cancer Cell |
| PubMed ID | 18394557 |
Related Faculty:
Juan Francisco Linares Rodriguez, Ph.D. Maria Diaz-Meco Conde, Ph.D.