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PMID:11060313

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Citation

Tan, KO, Tan, KM, Chan, SL, Yee, KS, Bevort, M, Ang, KC and Yu, VC (2001) MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J. Biol. Chem. 276:2802-7

Abstract

A novel Bax-associating protein, named MAP-1 (Modulator of Apoptosis), has been identified in a yeast two-hybrid screen. MAP-1 contains a BH3-like (BH: Bcl-2 homology) motif and mediates caspase-dependent apoptosis in mammalian cells when overexpressed. MAP-1 homodimerizes and associates with the proapoptotic Bax and the prosurvival Bcl-2 and Bcl-X(L) of the Bcl-2 family in vitro and in vivo in mammalian cells. Mutagenesis analyses revealed that the BH3-like domain in MAP-1 is not required for its association with Bcl-X(L) but is required for association with Bax and for mediating apoptosis. Interestingly, in contrast to other Bax-associating proteins such as Bcl-X(L) and Bid, which require the BH3 and BH1 domains of Bax, respectively, for binding, the binding of MAP-1 to Bax appears to require all three BH domains (BH1, BH2, and BH3) of Bax, because point mutation of the critical amino acid in any one of these domains is sufficient to abolish its binding to MAP-1. These data suggest that MAP-1 mediates apoptosis through a mechanism that involves binding to Bax.

Links

PubMed Online version:10.1074/jbc.M008955200

Keywords

Adaptor Proteins, Signal Transducing; Amino Acid Motifs; Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; Binding Sites; Carrier Proteins/genetics; Carrier Proteins/metabolism; Caspases/metabolism; Conserved Sequence; Dimerization; Humans; Mice; Molecular Sequence Data; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Sequence Homology, Amino Acid; bcl-2-Associated X Protein

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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