TMS1 peptide

ASC (apoptosis-associated speck-like protein containing a CARD) or TMS 1 (target of methylation-induced silencing) is a recently identified CpG island-associated gene that becomes hypermethylated and silenced in cells overexpressing DNA cytosine-5-methyltransferase-1. TMS1 is aberrantly methylated and silenced in human breast cancer cells. Forty percent (11 of 27) of primary breast tumors exhibited aberrant methylation of ASC. Ectopic expression of ASC induced apoptosis in 293 cells and inhibited the survival of human breast cancer cells. The methylation-mediated silencing of ASC may confer a survival advantage by allowing cells to escape from apoptosis, supporting a new role for aberrant methylation in breast tumorigenesis. ASC encodes a 22-kDa predicted protein containing a COOH-terminal caspase recruitment domain (CARD). However, it is structurally unrelated to other known CARD adaptor and regulatory proteins. Ectopic expression of ASC alone was able to trigger apoptosis in 293 cells, and cell death correlated with relocalization of ASC from the cytoplasm to perinuclear, ball-like structures. Several lines of evidence support the idea that redistribution of ASC is an intermediate step in a ASC-triggered apoptotic pathway.