The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation Export

@article{citeulike:5719288, abstract = {Akt signaling plays a central role in many biological functions, such as cell proliferation and apoptosis. Because Akt (also known as protein kinase B) resides primarily in the cytosol, it is not known how these signaling molecules are recruited to the plasma membrane and subsequently activated by growth factor stimuli. We found that the protein kinase Akt undergoes lysine-63 chain ubiquitination, which is important for Akt membrane localization and phosphorylation. TRAF6 was found to be a direct E3 ligase for Akt and was essential for Akt ubiquitination, membrane recruitment, and phosphorylation upon growth-factor stimulation. The human cancer-associated Akt mutant displayed an increase in Akt ubiquitination, in turn contributing to the enhancement of Akt membrane localization and phosphorylation. Thus, Akt ubiquitination is an important step for oncogenic Akt activation. 10.1126/science.1175065}, author = {Yang, Wei-Lei and Wang, Jing and Chan, Chia-Hsin and Lee, Szu-Wei and Campos, Alejandro D. and Lamothe, Betty and Hur, Lana and Grabiner, Brian C. and Lin, Xin and Darnay, Bryant G. and Lin, Hui-Kuan}, citeulike-article-id = {5719288}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1175065}, citeulike-linkout-1 = {http://www.sciencemag.org/content/325/5944/1134.abstract}, citeulike-linkout-2 = {http://www.sciencemag.org/content/325/5944/1134.full.pdf}, citeulike-linkout-3 = {http://www.sciencemag.org/cgi/content/abstract/325/5944/1134}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/19713527}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=19713527}, day = {28}, doi = {10.1126/science.1175065}, journal = {Science}, keywords = {akt, ligase, traf6, ubiquitination}, month = {August}, number = {5944}, pages = {1134--1138}, posted-at = {2009-10-12 16:11:21}, priority = {2}, title = {The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation}, url = {http://dx.doi.org/10.1126/science.1175065}, volume = {325}, year = {2009} }

TY - JOUR ID - citeulike:5719288 L3 - citeulike-article-id:5719288 N2 - Akt signaling plays a central role in many biological functions, such as cell proliferation and apoptosis. Because Akt (also known as protein kinase B) resides primarily in the cytosol, it is not known how these signaling molecules are recruited to the plasma membrane and subsequently activated by growth factor stimuli. We found that the protein kinase Akt undergoes lysine-63 chain ubiquitination, which is important for Akt membrane localization and phosphorylation. TRAF6 was found to be a direct E3 ligase for Akt and was essential for Akt ubiquitination, membrane recruitment, and phosphorylation upon growth-factor stimulation. The human cancer-associated Akt mutant displayed an increase in Akt ubiquitination, in turn contributing to the enhancement of Akt membrane localization and phosphorylation. Thus, Akt ubiquitination is an important step for oncogenic Akt activation. 10.1126/science.1175065 IS - 5944 JF - Science EP - 1138 TI - The E3 Ligase TRAF6 Regulates Akt Ubiquitination and Activation VL - 325 SP - 1134 KW - akt KW - ligase KW - traf6 KW - ubiquitination AU - Yang, Wei-Lei AU - Wang, Jing AU - Chan, Chia-Hsin AU - Lee, Szu-Wei AU - Campos, Alejandro AU - Lamothe, Betty AU - Hur, Lana AU - Grabiner, Brian AU - Lin, Xin AU - Darnay, Bryant AU - Lin, Hui-Kuan PY - 2009/08/28/ UR - http://dx.doi.org/10.1126/science.1175065 ER -