The BH3 Domain of Bcl-xS Is Required for Inhibition of the Antiapoptotic Function of Bcl-xL
AUTOR(ES)
Chang, Brian S.
FONTE
American Society for Microbiology
RESUMO
bcl-x is a member of the bcl-2 family of genes. The major protein product, Bcl-xL, is a 233-amino-acid protein which has antiapoptotic properties. In contrast, one of the alternatively spliced transcripts of the bcl-x gene codes for the protein Bcl-xS, which lacks 63 amino acids present in Bcl-xL and has proapoptotic activity. Unlike other proapoptotic Bcl-2 family members, such as Bax and Bak, Bcl-xS does not seem to induce cell death in the absence of an additional death signal. However, Bcl-xS does interfere with the ability of Bcl-xL to antagonize Bax-induced death in transiently transfected 293 cells. Mutational analysis of Bcl-xS was conducted to identify the domains necessary to mediate its proapoptotic phenotype. Deletion mutants of Bcl-xS which still contained an intact BH3 domain retained the ability to inhibit survival through antagonism of Bcl-xL. Bcl-xS was able to form heterodimers with Bcl-xL in mammalian cells, and its ability to inhibit survival correlated with the ability to heterodimerize with Bcl-xL. Deletion mutants of Bax and Bcl-2, which lacked BH1 and BH2 domains but contained a BH3 domain, were able to antagonize the survival effect conferred by Bcl-xL. The results suggest that BH3 domains from both pro- and antiapoptotic Bcl-2 family members, while lacking an intrinsic ability to promote programmed cell death, can be potent inhibitors of Bcl-xL survival function.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=84651Documentos Relacionados
- Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL.
- Heterogeneous Nuclear Ribonucleoprotein K Represses the Production of Pro-apoptotic Bcl-xS Splice Isoform
- Modulation of cell death by Bcl-xL through caspase interaction
- Expression of antiapoptotic genes bcl-xL and ced-9 in tomato enhances tolerance to viral-induced necrosis and abiotic stress
- Bcl-xL protects adult septal cholinergic neurons from axotomized cell death
