The role of ubiquitination and deubiquitination in PI3K/AKT/mTOR pathway: A potential target for cancer therapy

Abstract

The PI3K/AKT/mTOR pathway controls key cellular processes, including proliferation and tumor progression, and abnormally high activation of this pathway is a hallmark in human cancers. The post-translational modification, such as Ubiquitination and deubiquitination, fine-tuning the protein level and the activity of members in this pathway play a pivotal role in maintaining normal physiological process. Emerging evidence show that the unbalanced ubiquitination/deubiquitination modification leads to human diseases via PI3K/AKT/mTOR pathway. Therefore, a comprehensive understanding of the ubiquitination/deubiquitination regulation of PI3K/AKT/mTOR pathway may be helpful to uncover the underlying mechanism and improve the potential treatment of cancer via targeting this pathway. Herein, we summarize the latest research progress of ubiquitination and deubiquitination of PI3K/AKT/mTOR pathway, systematically discuss the associated crosstalk between them, as well as focus the clinical transformation via targeting ubiquitination process.

Keywords: Deubiquitination; PI3K/AKT/mTOR pathway; Targeted therapies; Ubiquitination.