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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
PTEN increases autophagy and inhibits the ubiquitin-proteasome pathway in glioma cells independently of its lipid phosphatase activity
PLoS ONE, Volume 8, No. 12, Article e83318, Year 2013
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Description
Two major mechanisms of intracellular protein degradation, autophagy and the ubiquitin-proteasome pathway, operate in mammalian cells. PTEN, which is frequently mutated in glioblastomas, is a tumor suppressor gene that encodes a dual specificity phosphatase that antagonizes the phosphatidylinositol 3-kinase class I/AKT/mTOR pathway, which is a key regulator of autophagy. Here, we investigated in U87MG human glioma cells the role of PTEN in the regulation of autophagy and the ubiquitin-proteasome pathway, because both are functionally linked and are relevant in cancer progression. Since U87MG glioma cells lack a functional PTEN, we used stable clones that express, under the control of a tetracycline-inducible system (Tet-on), wild-type PTEN and two of its mutants, G129EPTEN and C124S-PTEN, which, respectively, lack the lipid phosphatase activity only and both the lipid and the protein phosphatase activities of this protein. Expression of PTEN in U87MG glioma cells decreased proteasome activity and also reduced protein ubiquitination. On the contrary, expression of PTEN increased the autophagic flux and the lysosomal mass. Interestingly, and although PTEN negatively regulates the phosphatidylinositol 3-kinase class I/AKT/mTOR signaling pathway by its lipid phosphatase activity, both effects in U87MG cells were independent of this activity. These results suggest a new mTOR-independent signaling pathway by which PTEN can regulate in opposite directions the main mechanisms of intracellular protein degradation. © 2013 Errafiy et al.
Authors & Co-Authors
Errafiy, Rajaa
Spain, Valencia
Centro de Investigacion Principe Felipe
Morocco, Casablanca
Hassan Ii University of Casablanca
Aguado, Carmen
Spain, Valencia
Centro de Investigacion Principe Felipe
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Ghislat, Ghita
Spain, Valencia
Centro de Investigacion Principe Felipe
Esteve, Juan M.
Spain, Valencia
Centro de Investigacion Principe Felipe
Gil, Anabel
Spain, Valencia
Centro de Investigacion Principe Felipe
Loutfi, Mohammed
Morocco, Casablanca
Hassan Ii University of Casablanca
Knecht, Erwin
Spain, Valencia
Centro de Investigacion Principe Felipe
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Raras
Statistics
Citations: 67
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0083318
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics