BAX-ALPHA PERTURBS T-CELL DEVELOPMENT AND AFFECTS CELL-CYCLE ENTRY OFT-CELLS

Bax alpha can heterodimerize with Bcl-2 and Bcl-X(L), countering their effects, as well as promoting apoptosis on overexpression. We show th at bax alpha transgenic mice have greatly reduced numbers of mature T cells, which results from an impaired positive selection in the thymus , This perturbation in positive selection is accompanied by an increas e in the number of cycling thymocytes. Further to this, mature T cells overexpressing Bax alpha have lower levels of p27(Kip1) and enter S p hase more rapidly in response to interleukin-2 stimulation than do con trol T cells, while the converse is true of bcl-2 transgenic T cells, These data indicate that apoptotic regulatory proteins can modulate th e level of cell cycle-controlling proteins and thereby directly impact on the cell cycle.