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Review

Regulation of Akt signaling activation by ubiquitination

Wei-Lei Yang, Ching-Yuan Wu, Juan Wu and Hui-Kuan Lin

Akt (also known as PKB) signaling orchestrates many aspects of biological functions and, importantly, its deregulation is linked to cancer development. Akt activity is well-known regulated through its phosphorylation at T308 and S473 by PDK1 and mTORC2, respectively. Although in the last decade the research has been primarily focused on Akt phosphorylation and its role in Akt activation and functions, other posttranslational modifications on Akt have never been reported. Until very recently, a novel posttranslational modification on Akt termed ubiquitination was identified and shown to play an important role in Akt activation. The cancer-associated Akt mutant recently identified in a subset of human cancers displays enhanced Akt ubiquitination, in turn contributing to Akt hyperactivation, suggesting a potential role of Akt ubiquitination in cancers. Thus, this novel posttranslational modification on Akt reveals an exciting avenue that has advanced our current understandings of how Akt signaling activation is regulated.

Authors

Wei-Lei Yang

The University of Texas MD Anderson Cancer Center; Houston, TX

Ching-Yuan Wu

The University of Texas MD Anderson Cancer Center; Houston, TX

Juan Wu

The University of Texas MD Anderson Cancer Center; Houston, TX

Hui-Kuan Lin Corresponding author: hklin@mdanderson.org

The University of Texas MD Anderson Cancer Center; Houston, TX