title: Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO.
abstract: The occurrence of cancer is often associated with a dysfunction in one of the three central membrane-involution processes-autophagy, endocytosis or cytokinesis. Interestingly, all three pathways are controlled by the same central signaling module: the class III phosphatidylinositol 3-kinase (PI3K-III) complex and its catalytic product, the phosphorylated lipid phosphatidylinositol 3-phosphate (PtdIns3P). The activity of the catalytic subunit of the PI3K-III complex, the lipid-kinase VPS34, requires the presence of the membrane-targeting factor VPS15 as well as the adaptor protein Beclin 1. Furthermore, a growing list of regulatory proteins associates with VPS34 via Beclin 1. These accessory factors define distinct subunit compositions and thereby guide the PI3K-III complex to its different cellular and physiological roles. Here we discuss the regulation of the PI3K-III complex components by ubiquitination and SUMOylation. Especially Beclin 1 has emerged as a highly regulated protein, which can be modified with Lys11-, Lys48- or Lys63-linked polyubiquitin chains catalyzed by distinct E3 ligases from the RING-, HECT-, RBR- or Cullin-type. We also point out other cross-links of these ligases with autophagy in order to discuss how these data might be merged into a general concept.
authors.affiliation: Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, Bochum 44801, Germany. christina.reidick@rub.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Reidick
authors.affiliation: Biomedical Research, Human Brain Proteomics II, Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund 44139, Germany. fouzi.elmagraoui@isas.de.
authors.forename: Fouzi
authors.initials: F
authors.lastname: El Magraoui
authors.affiliation: Biomedical Research, Human Brain Proteomics II, Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund 44139, Germany. helmut.e.meyer@isas.de.
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo 0310, Norway. stenmark@ulrik.uio.no.
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
authors.affiliation: Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, Bochum 44801, Germany. harald.platta@rub.de.
authors.forename: Harald W
authors.initials: HW
authors.lastname: Platta