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Biochem Biophys Res Commun. 2008 May 9;369(3):964-8. doi: 10.1016/j.bbrc.2008.02.126. Epub 2008 Mar 6.

Role of AMP-activated protein kinase in autophagy and proteasome function.

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Instituto de Biomedicina de Valencia, CSIC, Nutrient signaling, Jaime Roig 11, 46010 Valencia, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), Valencia, Spain.


In this work, we have examined the possible role of AMP-activated protein kinase (a key energy sensor) in regulating intracellular protein degradation. We have found that AICAR, a known activator of AMPK, has a dual effect. On one hand, it inhibits autophagy by a mechanism independent of AMPK activity; AICAR decreases class III PI3-kinase binding to beclin-1 and this effect counteracts and reverses the known positive effect of AMPK activity on autophagy. On the other hand, AICAR inhibits the proteasomal degradation of proteins by an AMPK-dependent mechanism. This is a novel function of AMPK that allows the regulation of proteasomal activity under conditions of energy demand.

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