Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila.
BACKGROUND
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-beta1 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.


RESULTS
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.


CONCLUSIONS
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.
Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli-Strasse 16, 8093 Zurich, Switzerland.
Silvia
S
Gluderer
Erich
E
Brunner
Markus
M
Germann
Virginija
V
Jovaisaite
Changqing
C
Li
Cyrill A
CA
Rentsch
Ernst
E
Hafen
Hugo
H
Stocker
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D004175:Diptera / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development*; D029721:Drosophila Proteins / Q000502:physiology*; D006128:Growth / Q000235:genetics; D006801:Humans; D016350:Leucine Zippers / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C000608109:Madm protein, Drosophila; C410809:NRBP1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C099726:TSC22D1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D033921:Vesicular Transport Proteins; C529273:bun protein, Drosophila