After examining several other pathways we focused on activator protein 1 (AP-1) dependent transcription [41]. The classical AP-1 complex contains c-Jun and c-Fos, although other Jun proteins (JunB and JunD) and Fos proteins (Fra-1, Fra-2 and FosB) have also been reported [42]. Several studies reported that AP-1 induces apoptosis by activating pro-apoptotic genes [43–45]. For example, activation of AP-1 was reported in lymphoid cells after serum deprivation and this induction was associated with apoptosis [46]. Also, mouse knockout studies showed that JunB deficiency caused induction of B-cell leukemias [47]. Thus, we investigated whether Tcl1 can inhibit AP1-dependent transcription. Using reported system we showed that Tcl1 expression inhibited AP-1 dependent transactivation ~2.5-fold while Tcl1 T38I caused a dramatic ~100-fold inhibition, and the R52H mutant showed ~4 fold inhibition [23]. Similar results were obtained using individual components of the AP-1 complex, such as c-Jun, c-Fos and JunB. In all these cases Tcl1 T38I mutant inhibited more potently than WT Tcl1 strongly indicating that Tcl1 mutants show gain of function effect in AP-1 inhibition [23]. To elucidate the mechanism of this inhibition we
