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Cancers 2015, 7(1), 1-29; doi:10.3390/cancers7010001

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
2
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
Received: 31 October 2014 / Accepted: 8 December 2014 / Published: 23 December 2014
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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. View Full-Text
Keywords: VPS34; Beclin 1; Ambra 1; ubiquitin; SUMO; autophagy; tumor suppressor VPS34; Beclin 1; Ambra 1; ubiquitin; SUMO; autophagy; tumor suppressor
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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