WIP-ing out atherosclerosis with autophagy.
Atherosclerosis commonly causes coronary and cerebrovascular diseases, which are major morbidities worldwide. Controlling these conditions remains a challenge owing to an incomplete understanding of underlying molecular mechanisms. We have recently shown that PPM1D/WIP1 phosphatase plays a crucial role in regulating atherosclerosis in mice. Deletion of Ppm1d results in the suppression of lipid droplet accumulation in macrophages, which prevents the formation of foam cells, and ultimately the development of atherosclerotic plaques. This process is controlled by the ATM-MTOR pathway and depends on the activation of selective autophagy to regulate cholesterol efflux from macrophage foam cells. Our data suggest that modulating autophagy through the PPM1D-ATM-MTOR pathway may be beneficial at both early and advanced stages of atherosclerosis.
Institute of Molecular and Cell Biology, Proteos, Singapore.
Anna
A
Brichkina
Dmitry V
DV
Bulavin
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology*; D001343:Autophagy; D001692:Biological Transport; D018797:Cell Cycle Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D002784:Cholesterol; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C