title: The links between AKT and two intracellular proteolytic cascades: ubiquitination and autophagy.
abstract: The serine threonine kinase AKT plays a central role in the regulation of cell survival in a variety of human neoplastic diseases. A series of studies have revealed a connection between AKT signaling and two important protein degradation pathways in mammalian cells: the ubiquitin-proteasome system and autophagy. Two distinct ubiquitination systems have been reported to regulate AKT signaling: K63-linked ubiquitination, which promotes the oncogenic activation of AKT, and K48-linked ubiquitination, which triggers the proteasomal degradation of phosphorylated AKT. Autophagy is an evolutionarily conserved mechanism for the gross disposal and recycling of intracellular proteins in mammalian cells. AKT signaling may play a regulatory role in autophagy; however, the underlying mechanisms have not been fully clarified. Recently, AKT was shown to phosphorylate key molecules involved in the regulation of autophagy. Furthermore, lysosomal co-localization of the AKT-Phafin2 complex is reportedly critical for the induction of autophagy. In this review, we will discuss the connection between AKT, a core intracellular survival regulator, and two major intracellular proteolytic signaling pathways in mammalian cells.
authors.affiliation: Division of Cancer Biology Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. Electronic address: m_noguch@igm.hokudai.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Division of Cancer Biology Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hirata
authors.affiliation: Division of Cancer Biology Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Suizu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex
keywords: AKT; Autophagy; Ubiquitination