Characterization of a novel mouse cDNA, ES18, involved in apoptotic cell death of T-cells

Using the modified screening approach in combination with expressed sequenc e tags, we have identified several novel cDNAs from mouse embryonic stem (E S) cells, whose expression is tissue-restricted and/or developmentally regu lated. One of the cDNAs, ES18, is preferentially expressed in lymph node an d thymus, and contains noteworthy features of transcriptional regulator. Th e expression of ES18 transcript was selectively regulated during the apopto sis of T-cell thymoma S49.1 induced by several stimuli. Interestingly, the ES18 transcript was differently regulated in the mutually antagonistic proc ess, between dexamethasone- and A23187-induced cell death of T-cells, Moreo ver the message level of ES18 was selectively enhanced by staurosporine, a broad protein kinase inhibitor, but not by other protein kinase inhibitors such as GF109203X and H89, In addition, ES18 transcript was induced by Ca-c eramide, which is a mediator of both dexamethasone- and staurosporine-induc ed apoptotic signaling. We further showed that transient overexpression of ES18 in mouse T-cell lymphoma increased the apoptotic cell death. These dat a suggest that ES18 may be selectively involved in specific apoptotic proce sses in mouse T-cells.