Cloning studies have revealed that the apoptosis-associated speck-like
protein possessing a
caspase-recruiting domain (ASC) and the target of methylation-induced silencing-1 (TMS) are identical
proteins. ASC/TMS1 is a bipartite adaptor
protein containing the N-terminal pyrin domain and the C-terminal caspase-recruitment domain. There is abundant literature on ASC/TMS1, mostly under the name TMS1, in the epigenetic regulation of apoptosis and
carcinogenesis, whereas the abbreviation ASC has been adopted from studies on the assembly of
inflammasomes and stimulation of
inflammation. There is substantial literature emphasizing that there are common aspects in the regulation of apoptosis and
inflammation, which may be related to the function of ASC/TMS1. The region of the transcription start site of ASC/TMS1 gene contains a 600-bp-long CpG island that is highly methylated and the transcription of ASC/TMS1 is repressed in several
cancers. However, it is not known whether the ASC/TMS1-dependent epigenetic regulation controls the
inflammasome functions and moreover whether this regulation has any role in the
inflammation-mediated
carcinogenesis or in the pathogenesis of age-related degenerative diseases. We will examine the mechanisms involved in the epigenetic regulation of ASC/TMS1 as well as their significance in the coordination of apoptosis and
inflammasome functions. We will also review the role of aberrant methylation of ASC/TMS1 promoter in the function of
inflammasomes, a major host defense system, in cellular housekeeping and
carcinogenesis.