Bunched, the Drosophila Homolog of the Mammalian Tumor Suppressor TSC-22, Promotes Cellular Growth
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CitationGluderer, Silvia, Sean Oldham, Felix Rintelen, Andrea Sulzer, Corina Schütt, Xiaodong Wu, Laurel A. Raftery, Ernst Hafen, and Hugo Stocker. 2008. Bunched, the homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth. BMC Developmental Biology 8: 10.
AbstractBackground: Transforming Growth Factor-β1 stimulated clone-22 (TSC-22) is assumed to act as a negative growth regulator and tumor suppressor. TSC-22 belongs to a family of putative transcription factors encoded by four distinct loci in mammals. Possible redundancy among the members of the TSC-22/Dip/Bun protein family complicates a genetic analysis. In Drosophila, all proteins homologous to the TSC-22/Dip/Bun family members are derived from a single locus called bunched (bun). Results: We have identified bun in an unbiased genetic screen for growth regulators in Drosophila. Rather unexpectedly, bun mutations result in a growth deficit. Under standard conditions, only the long protein isoform BunA – but not the short isoforms BunB and BunC – is essential and affects growth. Whereas reducing bunA function diminishes cell number and cell size, overexpression of the short isoforms BunB and BunC antagonizes bunA function. Conclusion: Our findings establish a growth-promoting function of Drosophila BunA. Since the published studies on mammalian systems have largely neglected the long TSC-22 protein version, we hypothesize that the long TSC-22 protein is a functional homolog of BunA in growth regulation, and that it is antagonized by the short TSC-22 protein.
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