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Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO

1
Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, Bochum 44801, Germany
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Biomedical Research, Human Brain Proteomics II, Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund 44139, Germany
3
Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo 0310, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Hiromi I. Wettersten
Cancers 2015, 7(1), 1-29; https://doi.org/10.3390/cancers7010001
Received: 31 October 2014 / Accepted: 8 December 2014 / Published: 23 December 2014
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. View Full-Text
Keywords: VPS34; Beclin 1; Ambra 1; ubiquitin; SUMO; autophagy; tumor suppressor VPS34; Beclin 1; Ambra 1; ubiquitin; SUMO; autophagy; tumor suppressor
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Reidick, C.; El Magraoui, F.; Meyer, H.E.; Stenmark, H.; Platta, H.W. Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO. Cancers 2015, 7, 1-29.

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