The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
The Tumor Suppressor PTEN Positively Regulates Macroautophagy by Inhibiting the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway
Open accessAbstract
The tumor suppressor PTEN is a dual protein and phosphoinositide phosphatase that negatively controls the phosphatidylinositol (PI) 3-kinase/protein kinase B (Akt/PKB) signaling pathway. Interleukin-13 via the activation of the class I PI 3-kinase has been shown to inhibit the macroautophagic pathway in the human colon cancer HT-29 cells. Here we demonstrate that the wild-type PTEN is expressed in this cell line. Its overexpression directed by an inducible promoter counteracts the interleukin-13 down-regulation of macroautophagy. This effect was dependent upon the phosphoinositide phosphatase activity of PTEN as determined by using the mutant G129E, which has only protein phosphatase activity. The role of Akt/PKB in the signaling control of interleukin-13-dependent macroautophagy was investigated by expressing a constitutively active form of the kinase ((Myr)PKB). Under these conditions a dramatic inhibition of macroautophagy was observed. By contrast a high rate of autophagy was observed in cells expressing a dominant negative form of PKB. These data demonstrate that the signaling control of macroautophagy overlaps with the well known PI 3-kinase/PKB survival pathway and that the loss of PTEN function in cancer cells inhibits a major catabolic pathway.
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Cites
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Cited by
Regulation mechanisms and signaling pathways of autophagy
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Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
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Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice
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Metadata
- Authors
- Arico, S., Petiot, A., Bauvy, C., Dubbelhuis, P. F., Meijer, A. J., Codogno, P., & Ogier-Denis, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-09
- Volume
- 276
- Issue
- 38
- Pages
- 35243-35246
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2066030465
- Cited by
- 578
- References
- 6
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
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