Over-expression of a novel nuclear interactor of Suppressor of fused, the Drosophila myelodysplasia/myeloid leukaemia factor, induces abnormal morphogenesis associated with increased apoptosis and DNA synthesis.
BACKGROUND
In Drosophila and vertebrates, suppressor of fused (Su(fu)) proteins act as negative regulators of the Gli/Ci transcription factors, which mediate the transcriptional effects of Hh signalling.


RESULTS
We sought for novel partners of Su(fu) in fly using the two-hybrid method. Most of the Su(fu) interactors thus identified are (or are likely to be) able to enter the nucleus. We focused on one of these putative partners, dMLF, which resembles vertebrate myelodysplasia/myeloid leukaemia factors 1 and 2. We demonstrate that dMLF binds specifically to Su(fu) in vitro and in vivo. Using a novel anti-dMLF antibody, we showed, that dMLF is a nuclear, chromosome-associated protein. We over-expressed a dMLF transgene in fly using an inducible expression system and showed that dMLF over-expression disrupts normal development, leading to either a lethal phenotype or adult structural defects associated with apoptosis and increased DNA synthesis. Furthermore, the dMLF-induced eye phenotype is enhanced by the loss of Su(fu) function, suggesting a genetic interaction between Su(fu) and dMLF.


CONCLUSIONS
We propose that dSu(fu) and dMLF act together at the transcriptional level to coordinate patterning and proliferation during development.
Fouix
Sylvaine
S
Laboratoire de génétique du développement et évolution, Institut Jacques Monod, 2 Place Jussieu 75251 Paris, France.
Martin-Lannerée
Séverine
S
Sanial
Matthieu
M
Morla
Luciana
L
Lamour-Isnard
Claudie
C
Plessis
Anne
A
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001973:Bromodeoxyuridine; D002467:Cell Nucleus / Q000378:metabolism*; D002875:Chromosomes / Q000235:genetics; D004247:DNA / Q000096:biosynthesis*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development*; D005123:Eye / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009024:Morphogenesis; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D014158:Transcription, Genetic; D019076:Transgenes; D020798:Two-Hybrid System Techniques; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism
D029721:Drosophila Proteins; D011506:Proteins; D012097:Repressor Proteins; C490764:SUFU protein, human; C097059:Su(fu) protein, Drosophila; D004247:DNA; D001973:Bromodeoxyuridine