Kazemi-Esfarjani Parsa, Benzer Seymour
Department of Physiology and Biophysics, Center for Neuroscience, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
Hum Mol Genet. 2002 Oct 1;11(21):2657-72. doi: 10.1093/hmg/11.21.2657.
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.
特定蛋白质中异常长的聚谷氨酰胺[poly(Q)]序列的毒性是亨廷顿舞蹈病（HD）和其他几种遗传性神经退行性疾病共有的分子损伤。通过在果蝇中进行旨在发现抑制poly(Q)毒性基因的遗传筛选，我们发现了人类髓系白血病因子1（MLF1）的果蝇同源物。果蝇同源物（dMLF）的表达可改善在眼睛和中枢神经系统中表达的poly(Q)的毒性。在视网膜中，无论dMLF是内源性表达还是异位表达，它都与聚集体共定位，这表明dMLF单独或通过中间分子伴侣，可能通过隔离poly(Q)和/或其聚集体来抑制毒性。
