The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes.

Chen B, Borinstein SC, Gillis J, Sykes VW, Bogler O
J Biol Chem. 2000 275 (25): 19275-81

PMID: 10858458 · DOI:10.1074/jbc.M908994199

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 (19)

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 src Homology Domains Two-Hybrid System Techniques Ultraviolet Rays Xenopus

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