TMS1apoptosis-associated speck-like protein containing a CARD
TMS1 (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 (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 TMS1. Ectopic expression of TMS1 induced apoptosis in 293 cells and inhibited the survival of human breast cancer cells. The methylation-mediated silencing of TMS1 may confer a survival advantage by allowing cells to escape from apoptosis, supporting a new role for aberrant methylation in breast tumorigenesis. TMS1 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 TMS1 alone was able to trigger apoptosis in 293 cells, and cell death correlated with relocalization of TMS1 from the cytoplasm to perinuclear, ball-like structures. Several lines of evidence support the idea that redistribution of TMS1 is an intermediate step in a TMS1-triggered apoptotic pathway (2).
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