TMS1/ASC: the cancer connection.
TMS1/ASC is a bipartite protein comprising two protein-protein interaction domains, a pyrin domain (PYD) and a caspase recruitment domain (CARD). Proteins containing these domains play pivotal roles in regulating apoptosis and immune response pathways, and mutations in a number of PYD- and CARD-containing proteins have been linked to autoinflammatory diseases and cancer. Indeed, one of the ways in which TMS1/ASC was identified was as a target of methylation-mediated silencing in breast cancer cells. This review discusses the mounting evidence supporting a correlation between the silencing of TMS1/ASC expression and cancer. In addition, it addresses the reported functions of TMS1/ASC that include apoptosis, activation of inflammatory caspases and regulation of NF-kappa B, and discusses the potential ways in which loss of TMS1/ASC contributes to carcinogenesis.
McConnell
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BB
Department of Radiation Oncology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Vertino
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PM
D000818:Animals; D017209:Apoptosis; D053468:CARD Signaling Adaptor Proteins; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000502:physiology*; D019175:DNA Methylation; D004789:Enzyme Activation; D020868:Gene Silencing; D016678:Genome; D006801:Humans; D007249:Inflammation; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D000071198:Pyrin
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D016328:NF-kappa B; C402202:PYCARD protein, human; D011506:Proteins; D000071198:Pyrin; D020169:Caspases