The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4
- Author(s)
- Huang, DCS; Adams, JM; Cory, S;
- Details
- Publication Year 1998-02-16,Volume 17,Issue #4,Page 1029-1039
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- Abstract
- Bcl-2 and close homologues such as Bcl-x(L) promote cell survival, while other relatives such as Barr antagonize this function. Since only the pro-survival family members possess a conserved N-terminal region denoted BH4, me have explored the role of this amphipathic helix for their survival function and for interactions with several agonists of apoptosis, including Bax and CED-4, an essential regulator in the nematode Caenorhabditis elegans. BH4 of Bcl-2 could be replaced by that of Bcl-x without perturbing function but not by a somewhat similar region near the N-terminus of Bax. Bcl-2 cell survival activity was reduced by substitutions in two of ten conserved BH4 residues. Deletion of BH4 rendered Bcl-2 (and Bcl-x(L)) inactive but did not impair either Bcl-2 homodimerization or ability to bind to Bax or five other pro-apoptotic relatives (Bak, Bad, Bik, Bid or Bim), Hence, association with these death agonists is not sufficient to promote cell survival. Significantly, however, Bcl-x(L) lacking BH4 lost the ability both to bind CED-4 and antagonize its pro-apoptotic activity. These results favour the hypothesis that the BH4 domain of pro-survival Bcl-2 family members allows them to sequester CED-4 relatives and thereby prevent apoptosis.
- Publisher
- OXFORD UNIV PRESS
- Keywords
- PROGRAMMED CELL-DEATH; CAENORHABDITIS-ELEGANS; PROTEIN IDENTIFICATION; PROTOONCOGENE BCL-2; SEQUENCE SIMILARITY; E1B 19K; B-CELLS; GENE; SURVIVAL; FAMILY
- Publisher's Version
- https://doi.org/10.1093/emboj/17.4.1029
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1998-02-16 12:00:00