Bcl-xL/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry

Bcl‐x L and Bcl‐2 inhibit both apoptosis and proliferation. In investigating the relationship between these two functions of Bcl‐x L and Bcl‐2, an analysis of 24 Bcl‐x L and Bcl‐2 mutant alleles, including substitutions at residue Y28 previously reported to selectively abolish the cell cycle activity, showed that cell cycle delay and anti‐apoptosis co‐segregated in all cases. In determining whether Bcl‐2 and Bcl‐x L act in G 0 or G 1 , forward scatter and pyronin Y fluorescence measurements indicated that Bcl‐2 and Bcl‐x L cells arrested more effectively in G 0 than controls, and were delayed in G 0 –G 1 transition. The cell cycle effects of Bcl‐2 and Bcl‐x L were reversed by Bad, a molecule that counters the survival function of Bcl‐2 and Bcl‐x L . When control and Bcl‐x L cells of equivalent size and pyronin Y fluorescence were compared, the kinetics of cell cycle entry were similar, demonstrating that the ability of Bcl‐x L and Bcl‐2 cells to enhance G 0 arrest contributes significantly to cell cycle delay. Our data suggest that cell cycle effects and increased survival both result from intrinsic functions of Bcl‐2 and Bcl‐x L .