THE CELL-DEATH INHIBITOR BCL-2 AND ITS HOMOLOGS INFLUENCE CONTROL OF CELL-CYCLE ENTRY

The effect of the cell death inhibitor Bcl-2 and its homologues on cel l cycle regulation was explored in lymphocytes and cell lines. Express ion of a bcl-2 transgene reduced proliferation of thymocytes and delay ed cell cycle entry of mitogen-stimulated B and T lymphocytes. Overexp ression of Bcl-2, Bcl-x(L) or adenovirus E1B19kD substantially delayed serum stimulation-induced S phase entry of quiescent NIH 3T3 fibrobla sts. Bcl-2-mediated cell survival and growth inhibition are both antag onized by Bar. Bcl-2, Bcl-x(L) and E1B19kD, but not Bcl-2 mutants that are defective in blocking apoptosis, suppress growth of colon carcino ma cells. This evidence that regulation of cell survival is coupled to control of cell growth has implications for normal cell turnover and tumorigenesis.