Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO
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-II...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-12-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/7/1/1 |
| _version_ | 1797722524693299200 |
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| author | Christina Reidick Fouzi El Magraoui Helmut E. Meyer Harald Stenmark Harald W. Platta |
| author_facet | Christina Reidick Fouzi El Magraoui Helmut E. Meyer Harald Stenmark Harald W. Platta |
| author_sort | Christina Reidick |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T09:49:32Z |
| format | Article |
| id | doaj.art-dd2003a1149b4cbf8ca3afdca2178430 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T09:49:32Z |
| publishDate | 2014-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dd2003a1149b4cbf8ca3afdca21784302023-09-02T12:40:57ZengMDPI AGCancers2072-66942014-12-017112910.3390/cancers7010001cancers7010001Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMOChristina Reidick0Fouzi El Magraoui1Helmut E. Meyer2Harald Stenmark3Harald W. Platta4Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, Bochum 44801, GermanyBiomedical Research, Human Brain Proteomics II, Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund 44139, GermanyBiomedical Research, Human Brain Proteomics II, Leibniz-Institut für Analytische Wissenschaften-ISAS, Dortmund 44139, GermanyDepartment of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo 0310, NorwayBiochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, Bochum 44801, GermanyThe 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.http://www.mdpi.com/2072-6694/7/1/1VPS34Beclin 1Ambra 1ubiquitinSUMOautophagytumor suppressor |
| spellingShingle | Christina Reidick Fouzi El Magraoui Helmut E. Meyer Harald Stenmark Harald W. Platta Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO Cancers VPS34 Beclin 1 Ambra 1 ubiquitin SUMO autophagy tumor suppressor |
| title | Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO |
| title_full | Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO |
| title_fullStr | Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO |
| title_full_unstemmed | Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO |
| title_short | Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO |
| title_sort | regulation of the tumor suppressor function of the class iii phosphatidylinositol 3 kinase complex by ubiquitin and sumo |
| topic | VPS34 Beclin 1 Ambra 1 ubiquitin SUMO autophagy tumor suppressor |
| url | http://www.mdpi.com/2072-6694/7/1/1 |
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