Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila
1 Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli-Strasse 16, 8093 Zurich, Switzerland
2 Center for Model Organism Proteomes, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
3 Urology Research Laboratory, Departments of Urology and Clinical Research, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland
4 Institute of Zoology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
5 Current address: Department of Medicine, Epigenetics and Progenitor Cell Keystone Program, Fox Chase Cancer Center, Cottman Avenue 333, Philadelphia, PA 19111, USA
6 Current address: Urologische Universitätsklinik, Universitätsspital Basel, Spitalstrasse 21, 4031 Basel, Switzerland
Journal of Biology 2010, 9:9 doi:10.1186/jbiol216Published: 11 February 2010
The TSC-22 domain family (TSC22DF) consists of putative transcription factors harboring a DNA-binding TSC-box and an adjacent leucine zipper at their carboxyl termini. Both short and long TSC22DF isoforms are conserved from flies to humans. Whereas the short isoforms include the tumor suppressor TSC-22 (Transforming growth factor-β1 stimulated clone-22), the long isoforms are largely uncharacterized. In Drosophila, the long isoform Bunched A (BunA) acts as a growth promoter, but how BunA controls growth has remained obscure.
In order to test for functional conservation among TSC22DF members, we expressed the human TSC22DF proteins in the fly and found that all long isoforms can replace BunA function. Furthermore, we combined a proteomics-based approach with a genetic screen to identify proteins that interact with BunA. Madm (Mlf1 adapter molecule) physically associates with BunA via a conserved motif that is only contained in long TSC22DF proteins. Moreover, Drosophila Madm acts as a growth-promoting gene that displays growth phenotypes strikingly similar to bunA phenotypes. When overexpressed, Madm and BunA synergize to increase organ growth.
The growth-promoting potential of long TSC22DF proteins is evolutionarily conserved. Furthermore, we provide biochemical and genetic evidence for a growth-regulating complex involving the long TSC22DF protein BunA and the adapter molecule Madm.