The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation
| Autor: | Xin Lin, Szu Wei Lee, Jing Wang, Hui Kuan Lin, Wei Lei Yang, Chia Hsin Chan, Betty Lamothe, Alejandro D. Campos, Brian C. Grabiner, Lana Hur, Bryant G. Darnay |
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| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Cell signaling Ubiquitin-Protein Ligases Amino Acid Motifs Interleukin-1beta Transplantation Heterologous Apoptosis Biology Cell Line Mice Phosphatidylinositol Phosphates Cell Line Tumor Animals Humans Insulin-Like Growth Factor I Phosphorylation Protein kinase A Protein kinase B PI3K/AKT/mTOR pathway TNF Receptor-Associated Factor 6 Multidisciplinary Cell Membrane Ubiquitination Neoplasms Experimental Cell biology Ubiquitin ligase Transplantation biology.protein Cancer research Signal transduction Proto-Oncogene Proteins c-akt Neoplasm Transplantation Signal Transduction |
| Zdroj: | Science. 325:1134-1138 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.1175065 |
| Popis: | Regulating Akt The protein kinase Akt is activated in response to receptor-activated generation of the signaling second messenger phosphatidylinositol 3,4,5-trisphosphate and has roles in regulation of diverse processes from metabolism and cell survival to transcription and tumorigenesis. Yang et al. (p. 1134 ; see the Perspective by Restuccia and Hemmings ) report a previously unrecognized mode of regulation of Akt: covalent modification of Akt by linkage to lysine 63 of ubiquitin molecules. Such ubiquitination of Akt promotes localization to the cell membrane and consequent activation in cells stimulated with growth factors. TRAF6 (TNF receptor–associated factor 6) was implicated as the E3 ubiquitin ligase that mediates ubiquitination of Akt. Ubiquitination of Akt may influence its role in cancer cells: A mutant form of Akt associated with human cancer showed increased ubiquitination, and depletion of TRAF6 decreased tumorigenicity of a prostate cancer cell line in a mouse cancer model. |
| Databáze: | OpenAIRE |
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