| First Author | Pozuelo-Rubio M | Year | 2011 |
| Journal | Cell Death Differ | Volume | 18 |
| Issue | 3 | Pages | 479-92 |
| PubMed ID | 20885446 | Mgi Jnum | J:186326 |
| Mgi Id | MGI:5432048 | Doi | 10.1038/cdd.2010.118 |
| Citation | Pozuelo-Rubio M (2011) Regulation of autophagic activity by 14-3-3zeta proteins associated with class III phosphatidylinositol-3-kinase. Cell Death Differ 18(3):479-92 |
| abstractText | 14-3-3s are binding proteins with survival functions in cells by interaction with proteins involved in the regulation of cell fate. The role of 14-3-3 during autophagy was investigated, thus, a forced expression of 14-3-3zeta reduces C2-ceramide-induced autophagy, whereas depletion of 14-3-3zeta promotes autophagy. The 14-3-3 role in autophagyc-related proteins was also investigated. The human vacuolar protein sorting 34 (hVps34), the class III phosphatidylinositol-3-kinase mediates multiple vesicle-trafficking processes such as endocytosis and autophagy, its activation being a requirement for autophagy initiation. Using chromatography techniques, hVps34 were eluted from a 14-3-3 affinity column, showing also a direct interaction with 14-3-3 proteins under physiological condition. Further analysis suggests that hVps34/14-3-3 association is a phorbol-12-myristate-13-acetate-dependent phosphorylated mechanism promoting a strong inhibition of the hVps34 lipid kinase activity, proteins kinase C being the likely kinase involved in phosphorylation and 14-3-3 binding of hVps34 under physiological conditions. Meanwhile, stimulation of autophagy leads to the dissociation of the 14-3-3/hVps34 complex enhancing hVps34 lipid kinase activity. Forced expression of 14-3-3zeta reduces hVps34 kinase activity and depletion of 14-3-3zeta promotes upregulation of this activity. In this study, 14-3-3zeta proteins are shown as a negative regulator of autophagy through regulation of a key component of early stages of the autophagy pathway, such as hVps34. |
