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PMID:11527400

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Citation

Antoku, K, Maser, RS, Scully, WJ Jr, Delach, SM and Johnson, DE (2001) Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and suppressor of death domains protein. Biochem. Biophys. Res. Commun. 286:1003-10

Abstract

The Bcl-2 oncoprotein is a potent inhibitor of apoptosis and is overexpressed in a variety of different malignancies. Bcl-2 function is regulated through heterodimerization with other members of the Bcl-2 protein family. In addition, several proteins that are not members of the Bcl-2 family can bind to Bcl-2, including BAG-1 protein. In this study, we screened for proteins that bind to Bcl-2, and isolated two additional members of the BAG-1 protein family, BAG-3 and BAG-4. The BAG-4 protein that we cloned also corresponds to the recently isolated suppressor of death domains (SODD) protein, a molecule that binds and inhibits signaling by tumor necrosis factor receptor 1 (TNFR1). Both BAG-3 and BAG-4/SODD were found to physically associate with Bcl-2, and both proteins are well conserved from human to mouse. A region of homology, comprising 68 amino acids, is present in the carboxyl termini of BAG-3 and BAG-4/SODD, and this region corresponds with sequences termed BAG domains that are found in other members of the BAG-1 protein family. In BAG-3 and BAG-4/SODD, the BAG domains appear to constitute the Bcl-2 binding regions of these molecules. BAG-3 and BAG-4/SODD, like BAG-1, were also shown to bind to Hsp70 inside the cell. Moreover, BAG-3 overexpression modestly inhibited apoptosis resulting from cytokine deprivation of IL-3-dependent 32D cells. Together, our findings demonstrate that other members of the BAG-1 protein family, namely BAG-3 and BAG-4/SODD, bind to Bcl-2 and provide a potential link between pathways regulated by Bcl-2 and pathways regulated by Hsp70, as well as TNFR1.

Links

PubMed Online version:10.1006/bbrc.2001.5512

Keywords

Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Antigens, CD/metabolism; Baculoviridae/metabolism; Carrier Proteins/chemistry; Carrier Proteins/isolation & purification; Cell Line; Cloning, Molecular; Conserved Sequence; DNA, Complementary/metabolism; DNA-Binding Proteins; Gene Library; HSP70 Heat-Shock Proteins/metabolism; Humans; Insects; Interleukin-3/metabolism; Mice; Molecular Sequence Data; Multigene Family; Precipitin Tests; Protein Binding; Protein Biosynthesis; Protein Structure, Tertiary; Proto-Oncogene Proteins c-bcl-2/chemistry; Proto-Oncogene Proteins c-bcl-2/metabolism; Receptors, Tumor Necrosis Factor/metabolism; Receptors, Tumor Necrosis Factor, Type I; Recombinant Fusion Proteins/metabolism; Sequence Homology, Amino Acid; Signal Transduction; Transcription Factors; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HS71B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CI61
PR:Q9JLV1

F

Seeded From UniProt

complete

MOUSE:BAG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P17879

F

Seeded From UniProt

complete

MOUSE:BAG3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P17879

F

Seeded From UniProt

complete

MOUSE:BAG3

acts_upstream_of_or_within

GO:0097192: extrinsic apoptotic signaling pathway in absence of ligand

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:IL3

acts_upstream_of_or_within

GO:0097192: extrinsic apoptotic signaling pathway in absence of ligand

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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