Characterization of the Drosophila myeloid leukemia factor.
In human, the myeloid leukemia factor 1 (hMLF1) has been shown to be involved in acute leukemia, and mlf related genes are present in many animals. Despite their extensive representation and their good conservation, very little is understood about their function. In Drosophila, dMLF physically interacts with both the transcription regulatory factor DREF and an antagonist of the Hedgehog pathway, Suppressor of Fused, whose over-expression in the fly suppresses the toxicity induced by polyglutamine. No connection between these data has, however, been established. Here, we show that dmlf is widely and dynamically expressed during fly development. We isolated and analyzed the first dmlf mutants: embryos lacking maternal dmlf product have a low viability with no specific defect, and dmlf(-)- adults display weak phenotypes. We monitored dMLF subcellular localization in the fly and cultured cells. We were able to show that, although generally nuclear, dMLF can also be cytoplasmic, depending on the developmental context. Furthermore, two differently spliced variants of dMLF display differential subcellular localization, allowing the identification of regions of dMLF potentially important for its localization. Finally, we demonstrate that dMLF can act developmentally and postdevelopmentally to suppress neurodegeneration and premature aging in a cerebellar ataxia model.
Martin-Lannerée
Séverine
S
Laboratoire de Génétique du Développement et Evolution, Institut Jacques Monod, UMR 7592 CNRS Université Paris 6 et Paris 7, 2 place Jussieu, 75 251 Paris Cedex 05, France.
Lasbleiz
Christelle
C
Sanial
Matthieu
M
Fouix
Sylvaine
S
Besse
Florence
F
Tricoire
Hervé
H
Plessis
Anne
A
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D005123:Eye / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; C468117:Mlf protein, Drosophila; D020033:Protein Isoforms; D012097:Repressor Proteins; C097059:Su(fu) protein, Drosophila; D014157:Transcription Factors