Gluderer, S., Oldham, S., Rintelen, F., Sulzer, A., Schütt, C., Wu, X., Raftery, L.A., Hafen, E., Stocker, H. (2008). Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth.  BMC Dev. Biol. 8(): 10.

FBrf0205279

Research paper

Transforming Growth Factor-beta1 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).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.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.

PMC2253523 (PMC) (EuropePMC)