Suppression of polyglutamine toxicity by a Drosophila homolog of myeloid leukemia factor 1.
The toxicity of an abnormally long polyglutamine [poly(Q)] tract within specific proteins is the molecular lesion shared by Huntington's disease (HD) and several other hereditary neurodegenerative disorders. By a genetic screen in Drosophila, devised to uncover genes that suppress poly(Q) toxicity, we discovered a Drosophila homolog of human myeloid leukemia factor 1 (MLF1). Expression of the Drosophila homolog (dMLF) ameliorates the toxicity of poly(Q) expressed in the eye and central nervous system. In the retina, whether endogenously or ectopically expressed, dMLF co-localized with aggregates, suggesting that dMLF alone, or through an intermediary molecular partner, may suppress toxicity by sequestering poly(Q) and/or its aggregates.
D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism* / Q000633:toxicity*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; C468117:Mlf protein, Drosophila; D010455:Peptides; D011506:Proteins; D014157:Transcription Factors; C097188:polyglutamine