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 carried out a series of co-immunoprecipitation experiments. These results revealed that Tcl1 specifically interacts with c-Jun, c-Fos and JunB. Thus, we concluded that Tcl1 physically interacts with AP-1 components and functions as an AP-1 inhibitor [23]. The fact that both Tcl1 mutants identified in CLL patients show gain of function properties in this pathway suggests the ability of Tcl1 to inhibit AP-1 dependent transcription is critical in the pathogenesis of CLL (Figure 2).
