[PDF][PDF] Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1

PF Dijkers, RH Medema, JWJ Lammers… - Current Biology, 2000 - cell.com
PF Dijkers, RH Medema, JWJ Lammers, L Koenderman, PJ Coffer
Current Biology, 2000cell.com
Cell death is regulated mainly through an evolutionarily conserved form of cell suicide
termed apoptosis [1]. Deregulation of apoptosis has been associated with cancer,
autoimmune diseases and degenerative disorders. Many cells, particularly those of the
hematopoietic system, have a default program of cell death and survival that is dependent
on the constant supply of survival signals. The Bcl-2 family, which has both pro-and anti-
apoptotic members, plays a critical role in regulating cell survival [2]. One family member, the …
Abstract
Cell death is regulated mainly through an evolutionarily conserved form of cell suicide termed apoptosis [1]. Deregulation of apoptosis has been associated with cancer, autoimmune diseases and degenerative disorders. Many cells, particularly those of the hematopoietic system, have a default program of cell death and survival that is dependent on the constant supply of survival signals. The Bcl-2 family, which has both pro- and anti-apoptotic members, plays a critical role in regulating cell survival [2]. One family member, the Bcl-2 interacting mediator of cell death (Bim), contains only a protein-interaction motif known as the BH3 domain, allowing it to bind pro-survival Bcl-2 molecules, neutralizing their function [3]. Disruption of the bim gene results in resistance to apoptosis following cytokine withdrawal in leukocytes, indicating that regulation of the pro-apoptotic activity of Bim is critical for maintenance of the default apoptotic program [4]. Here, we report that withdrawal of cytokine results in upregulation of Bim expression concomitant with induction of the apoptotic program in lymphocytes. Activation of the forkhead transcription factor FKHR-L1, previously implicated in regulation of apoptosis in T lymphocytes [5], was sufficient to induce Bim expression. We propose a mechanism by which cytokines promote lymphocyte survival by inhibition of FKHR-L1, preventing Bim expression.
cell.com