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Developmental expression and phylogenetic conservation of alternatively spliced forms of the C-terminal binding protein corepressor

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Abstract

The C-terminal binding protein (CtBP) is an evolutionarily conserved transcriptional corepressor found in multicellular eukaryotes. Multiple forms of the protein are typically found in animal cells, produced from separate genes and by alternative splicing. CtBP isoforms have also been implicated in cytoplasmic functions, including Golgi fission and vesicular trafficking. All forms of CtBP contain a conserved core domain that is homologous to α-hydroxyacid dehydrogenases, and a subset of isoforms (CtBPL) contain extensions at the C terminus. Despite distinct developmental profiles and knockout phenotypes in the mouse, the properties of different isoforms of the protein are found to be similar in many transcriptional assays. We have investigated the expression and conservation of distinct isoforms of the CtBP protein in insects and found that the expression of multiple, developmentally regulated isoforms is widely conserved. In a variety of Drosophila species, the relative abundance of CtBPL to CtBPS drops sharply after embryogenesis, revealing a conserved developmental shift. Despite the overall lower levels of this isoform, bioinformatic analysis reveals that exons encoding the C-terminal extension in CtBPL are conserved from Diptera to Coleoptera, suggesting that the CtBPL isoform contributes an important, evolutionarily conserved function.

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Acknowledgments

We thank Scott Pitnick, Susan Brown, Zachary Huang, Ned Walker, and Tucson Drosophila Stock Center for flies and insects used in this study and Dr. Casey Bergman for advice on alignments, and two anonymous reviewers for their helpful suggestions. We thank Paolo Struffi for generating the anti-CtBP antibody, as described in Struffi and Arnosti (2005), and Montserrat Sutrias-Grau for pointing out the potential SUMOylation sequences in CtBPL. This project was supported by NIH GM56976 to D.N.A.

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Correspondence to David N. Arnosti.

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Communicated by P. Simpson

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Mani-Telang, P., Arnosti, D.N. Developmental expression and phylogenetic conservation of alternatively spliced forms of the C-terminal binding protein corepressor. Dev Genes Evol 217, 127–135 (2007). https://doi.org/10.1007/s00427-006-0121-4

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