title: Posttranslational regulation of Akt in human cancer.
abstract: 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.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11790 USA.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Chan
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11790 USA.
authors.forename: Ukhyun
authors.initials: U
authors.lastname: Jo
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11790 USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Kohrman
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.
authors.forename: Abdol Hossein
authors.initials: AH
authors.lastname: Rezaeian
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA.
authors.forename: Ping-Chieh
authors.initials: PC
authors.lastname: Chou
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Logothetis
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA ; Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030 USA ; Graduate Institute of Basic Medical Science, China Medical University, Taichung, 404 Taiwan ; Department of Biotechnology, Asia University, Taichung, 404 Taiwan.
authors.forename: Hui-Kuan
authors.initials: HK
authors.lastname: Lin
keywords: Akt; Cancer therapy; K63-linked ubiquitination; Posttranslational modification