The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes.
Expression of the src homology 3 (SH3) domain-containing expressed in tumorigenic astrocytes (SETA) gene is associated with the tumorigenic state in astrocytes. SETA encodes a variety of adapter proteins containing either one or two SH3 domains, as suggested by the sequence heterogeneity of isolated cDNAs. Using both SH3 domains in ... a yeast two-hybrid screen of a glial progenitor cell cDNA library, we isolated the rat homolog of the ALG-2-interacting protein 1 or ALG-2-interacting protein X (AIP1/Alix). In vitro confrontation experiments showed that the SH3-N domain of SETA interacted with the proline-rich C terminus of AIP1. In co-immunoprecipitation experiments, SETA and AIP1 interacted and could form a complex with apoptosis-linked gene 2 protein. Endogenous SETA and AIP1 proteins showed similar patterns of staining in primary rat astrocytes. Misexpression of a variety of SETA protein isoforms in these astrocytes revealed that they localized to the actin cytoskeleton. Furthermore, SETA proteins containing the SH3-N domain were able to sensitize astrocytes to apoptosis induced by UV irradiation. Expression of the isolated SH3-N domain had the greatest effect in these experiments, indicating that interference in the interaction between endogenous SETA and AIP1 sensitizes astrocytes to apoptosis in response to DNA damage.
Mesh Terms:
Actins, Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Astrocytes, Calcium-Binding Proteins, Carrier Proteins, DNA, Complementary, Molecular Sequence Data, Neoplasm Proteins, Nerve Tissue Proteins, Protein Binding, Rats, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Ultraviolet Rays, Xenopus, src Homology Domains
Actins, Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Astrocytes, Calcium-Binding Proteins, Carrier Proteins, DNA, Complementary, Molecular Sequence Data, Neoplasm Proteins, Nerve Tissue Proteins, Protein Binding, Rats, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Ultraviolet Rays, Xenopus, src Homology Domains
J. Biol. Chem.
Date: Jun. 23, 2000
PubMed ID: 10858458
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