Promyelocytic Leukemia protein (PML) interacts with ASC to limit Inflammasome Activation [Signal Transduction]

January 9th, 2014 by Dowling, J. K., Becker, C. E., Bourke, N. M., Corr, S. C., Connolly, D. J., Quinn, S. R., Pandolfi, P. P., Mansell, A., O'Neill, L. A. J.

The apoptosis associated speck-like protein containing a CARD (ASC) is an essential component of several inflammasomes, multiprotein complexes that regulate caspase-1 activation and inflammation. We report here an interaction between promyelocytic leukemia protein (PML) and ASC. We observed enhanced formation of ASC dimers in PML- deficient macrophages. These macrophages also display enhanced levels of ASC in the cytosol. Furthermore, IL-1β production was markedly enhanced in these macrophages in response to both NLRP3 and AIM2 inflammasome activation and following BMDM infection with herpes simplex virus-1 (HSV-1) and Salmonella typhimurium. Collectively our data indicate that PML limits ASC function, retaining ASC in the nucleus.