期刊
CELL AND BIOSCIENCE
卷 4, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/2045-3701-4-59
关键词
Akt; Posttranslational modification; K63-linked ubiquitination; Cancer therapy
资金
- NCI Transition Career Development Award from National Institute of Health
- Stony Brook University New Investigator Fund
- NIH
- University of Texas MD Anderson Prostate Cancer Moon Shots Program
- R. Lee Clark fund
- MD Anderson prostate spore development grant
- MD Anderson prostate spore grant
Akt regulates critical cellular processes including cell survival and proliferation, glucose metabolism, cell migration, cancer progression and metastasis through phosphorylation of a variety of downstream targets. The Akt pathway is one of the most prevalently hyperactivated signaling pathways in human cancer, thus, research deciphering molecular mechanisms which underlie the aberrant Akt activation has received enormous attention. The PI3K-dependent Akt serine/threonine phosphorylation by PDK1 and mTORC2 has long been thought to be the primary mechanism accounting for Akt activation. However, this regulation alone does not sufficiently explain how Akt hyperactivation can occur in tumors with normal levels of PI3K/PTEN activity. Mounting evidence demonstrates that aberrant Akt activation can be attributed to other posttranslational modifications, which include tyrosine phosphorylation, O-GlcNAcylation, as well as lysine modifications: ubiquitination, SUMOylation and acetylation. Among them, K63-linked ubiquitination has been shown to be a critical step for Akt signal activation by facilitating its membrane recruitment. Deficiency of E3 ligases responsible for growth factor-induced Akt activation leads to tumor suppression. Therefore, a comprehensive understanding of posttranslational modifications in Akt regulation will offer novel strategies for cancer therapy.
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