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

AUTOR(ES)

Janumyan, Yelena M.

FONTE

Oxford University Press

RESUMO

Bcl-xL and Bcl-2 inhibit both apoptosis and proliferation. In investigating the relationship between these two functions of Bcl-xL and Bcl-2, an analysis of 24 Bcl-xL 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-xL act in G0 or G1, forward scatter and pyronin Y fluorescence measurements indicated that Bcl-2 and Bcl-xL cells arrested more effectively in G0 than controls, and were delayed in G0–G1 transition. The cell cycle effects of Bcl-2 and Bcl-xL were reversed by Bad, a molecule that counters the survival function of Bcl-2 and Bcl-xL. When control and Bcl-xL cells of equivalent size and pyronin Y fluorescence were compared, the kinetics of cell cycle entry were similar, demonstrating that the ability of Bcl-xL and Bcl-2 cells to enhance G0 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-xL.

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