Research article

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

Silvia Gluderer¹ , Sean Oldham^2,5 , Felix Rintelen^2,6 , Andrea Sulzer² , Corina Schütt³ , Xiaodong Wu⁴ , Laurel A Raftery⁴ , Ernst Hafen¹ and Hugo Stocker¹

¹  Institute of Molecular Systems Biology, ETH Zürich, Wolfgang-Pauli-Str. 16, 8093 Zürich, Switzerland

²  Zoological Institute, University of Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland

³  The Genetics Company Inc., Wagistr. 27, 8952 Schlieren, Switzerland

⁴  Cutaneous Biology Research Center, Massachusetts General Hospital/Harvard Med. School, Charlestown, MA 02129, USA

⁵  Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA

⁶  PFC Pharma Focus AG, Chriesbaumstr. 2, 8604 Volketswil, Switzerland

author email corresponding author email

BMC Developmental Biology 2008, 8:10doi:10.1186/1471-213X-8-10

Published:	28 January 2008

Abstract

Background

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.