To reveal the molecular mechanism of cellular senescence, we have surveyed the genes that are specifically upregulated via MEFs senescence by Suppression subtractive hybridization method. We show here that mTARSH was induced particularly in the relative early phase of MEFs cellular senescence. Further structural analysis of mTARSH disclosed five splicing variants shared a common reading frame whose diversity was derived from the SH3-binding motif cluster in the middle of the gene. We also show that mTARSH mRNA predominantly expressed in lung and that conspicuous expression of TARSH was drastically declined in all several lung cancer cell lines we tested. Thus, TARSH presumably represents a trigger gene for evoking cellular senescence, which has also been suggested to be involved in the prevention of tumorigenesis. (c) 2005 Elsevier Inc. All rights reserved.