Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth.
BACKGROUND
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).


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.


CONCLUSIONS
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.
Gluderer
Silvia
S
Institute of Molecular Systems Biology, ETH Zürich, Wolfgang-Pauli-Str, 16, 8093 Zürich, Switzerland. gluderer@imsb.biol.ethz.ch
Oldham
Sean
S
Rintelen
Felix
F
Sulzer
Andrea
A
Schütt
Corina
C
Wu
Xiaodong
X
Raftery
Laurel A
LA
Hafen
Ernst
E
Stocker
Hugo
H
D000483:Alleles; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000235:genetics*; D048429:Cell Size; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D017344:Genes, Insect; D005809:Genes, Regulator; D005838:Genotype; D009154:Mutation; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1