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The E3 ligase TRAF6 regulates Akt ubiquitination and activation.

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.

SUBMITTER: Yang WL

PROVIDER: S-EPMC3008763 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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The E3 ligase TRAF6 regulates Akt ubiquitination and activation.

Yang Wei-Lei WL Wang Jing J Chan Chia-Hsin CH Lee Szu-Wei SW Campos Alejandro D AD Lamothe Betty B Hur Lana L Grabiner Brian C BC Lin Xin X Darnay Bryant G BG Lin Hui-Kuan HK

Science (New York, N.Y.) 20090801 5944

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 direc ...[more]

PMID: 19713527

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Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling

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