Evidence for sequestration of polyglutamine inclusions by Drosophila myeloid leukemia factor.
Intracellular inclusions of abnormally long polyglutamine tracts and neurotoxicity are the hallmarks of several hereditary neurodegenerative disorders, including Huntington's disease (HD). In Drosophila melanogaster, dMLF, an ortholog of human myeloid leukemia factors, hMLF1 and hMLF2, suppressed polyglutamine toxicity and colocalized with the inclusions. In transfected primary rat neuronal cultures, dMLF and its orthologs reduced the morphological phenotypes and inclusions. Furthermore, dMLF reduced the recruitment of CBP and Hsp70 into the inclusions, both of which are among many essential proteins apparently trapped in the inclusions. These data suggest that a possible mechanism of suppression by dMLF is via the sequestration of polyglutamine oligomers or inclusions.
Kim
Woo-Yang
WY
Department of Pharmacology and Toxicology, Center for Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
Fayazi
Zahra
Z
Bao
Xiankun
X
Higgins
Dennis
D
Kazemi-Esfarjani
Parsa
P
D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; C100852:MLF1 protein, human; C100853:MLF2 protein, human; C468117:Mlf protein, Drosophila; D009687:Nuclear Proteins; D010455:Peptides; D011506:Proteins; D012097:Repressor Proteins; C097188:polyglutamine