Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation.

Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation. Research Abstract Details 

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Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation. Abstract Text:

(1)Pten (phosphatase and tensin homolog deleted on chromosome ten), a tumor suppressor, is a phosphatase with a variety of substrate specificities. Its function as a negative regulator of the class I phosphatidyl-inositol 3-kinase/Akt pathway antagonizes insulin-dependent cell signaling. The targeted deletion of Pten in mouse liver leads to insulin hypersensitivity and the upregulation of the phosphatidyl-inositol 3-kinase/Akt signaling pathway. In this study, we investigated the effects of Pten deficiency on autophagy, a major cellular degradative system responsible for the turnover of cell constituents. The autophagic degradation of [(14)C-leucine-labeled proteins of hepatocytes isolated from Pten-deficient livers was strongly inhibited, compared with that of control hepatocytes. However, no significant difference was found in the levels of the Atg12-Atg5 conjugate and LC3-II, the lipidated form of LC3, an intrinsic autophagosomal membrane marker, between control and Pten-deficient livers. Electron microsopic analyses showed that numerous autophagic vacuoles (autophagosomes plus autolysosomes) were present in the livers of control mice that had been starved for 48 hours, whereas they were markedly reduced in Pten-deficient livers under the same conditions. In vivo administration of leupeptin to control livers caused the inhibition of autophagic proteolysis, resulting in the accumulation of autolysosomes. These autolysosomes could be separated as a denser autolysosomal fraction from other cell membranes by Percoll density gradient centrifugation. In leupeptin-administered mutant livers, however, the accumulation of denser autolysosomes was reduced substantially. Collectively, we conclude that enhanced insulin signaling in Pten deficiency suppresses autophagy at the formation and maturation steps of autophagosomes, without inhibiting ATG conjugation reactions.

Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation. Publishing Authors By Initials

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Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Autophagy

VOLUME: 4

Page Numbers: 692-700

Journal Abbreviation: Autophagy

ISSN: 1554-8635

DAY: 10

MONTH: 04

YEAR: 2008

Loss of Pten, a tumor suppressor, causes the strong inhibition of autophagy without affecting LC3 lipidation. Information

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LANGUAGE: eng

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Country: United States

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MEDLINETA: Autophagy

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