PUBLICATION
Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis
- Authors
- Bae, J., Hsu, S.Y., Leo, P., Zell, K., and Hsueh, A.J.
- ID
- ZDB-PUB-010813-1
- Date
- 2001
- Source
- Apoptosis : an international journal on programmed cell death 6(5): 319-330 (Journal)
- Registered Authors
- Keywords
- apoptosis, Bcl-2, BAD, phosphorylation, programmed cell death, yeast two-hybrid
- MeSH Terms
-
- bcl-Associated Death Protein
- Cricetinae
- Humans
- Conserved Sequence
- Binding Sites
- Molecular Sequence Data
- Sequence Homology, Amino Acid
- Proto-Oncogene Proteins c-bcl-2/metabolism*
- Escherichia coli/genetics
- Phosphorylation
- Transfection
- Apoptosis*
- Tyrosine 3-Monooxygenase/metabolism
- Amino Acid Sequence
- Evolution, Molecular
- Yeasts/genetics
- Zebrafish Proteins
- Animals
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Carrier Proteins/physiology*
- 14-3-3 Proteins
- Two-Hybrid System Techniques
- CHO Cells
- PubMed
- 11483855 Full text @ Apoptosis
Citation
Bae, J., Hsu, S.Y., Leo, P., Zell, K., and Hsueh, A.J. (2001) Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. Apoptosis : an international journal on programmed cell death. 6(5):319-330.
Abstract
Survival factors activate kinases which, in turn, phosphorylate the proapoptotic Bcl-xl/Bcl-2-associated death promoter homolog (BAD) protein at key serine residues. Phosphorylated BAD interacts with 14-3-3 proteins, and overexpression of 14-3-3 attenuates BAD-mediated apoptosis. Although BAD is known to interact with Bcl-2, Bcl-w, and Bcl-xL, the exact relationship between BAD and anti- or proapoptotic Bcl-2 proteins has not been analyzed systematically. Using the yeast two-hybrid protein interaction assay, we found that BAD interacted negligibly with proapoptotic Bcl-2 proteins. Even though wild type BAD only interacted with selected numbers of antiapoptotic proteins, underphosphorylated mutant BAD interacted with all antiapoptotic Bcl-2 proteins tested (Bcl-2, Bcl-w, Bcl-xL, Bfl-1/A1, Mcl-1, Ced-9, and BHRF-1). Using nonphosphorylated recombinant BAD expressed in bacteria, direct interactions between BAD and diverse antiapoptotic Bcl-2 members were also observed. Furthermore, apoptosis induced by BAD was blocked by coexpression with Bcl-2, Bcl-w, and Bfl-1. Comparison of BAD orthologs from zebrafish to human indicated the conservation of a 14-3-3 binding site and the BH3 domain during evolution. Thus, highly conserved BAD interacts with diverse antiapoptotic Bcl-2 members to regulate apoptosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping