The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB that blocks TNFα-induced apoptosis
- Center for Advanced Biotechnology and Medicine, Graduate Program in Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School (UMDNJ–RWJMS), Graduate Program in Microbiology and Molecular Genetics, Rutgers University, Department of Biochemistry, UMDNJ–RWJMS, Piscataway, New Jersey 08854-5638 USA
Abstract
Bcl-2-family proteins are key regulators of the apoptotic response. Here, we demonstrate that the pro-survival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB. We show that bfl-1 gene expression is dependent on NF-κB activity and that it can substitute for NF-κB to suppress TNFα-induced apoptosis. bfl-1 promoter analysis identified an NF-κB site responsible for its Rel/NF-κB-dependent induction. The expression of bfl-1 in immune tissues supports the protective role of NF-κB in the immune system. The activation of Bfl-1 may be the means by which NF-κB functions in oncogenesis and promotes cell resistance to anti-cancer therapy.
