生物
蛋白酶体
神经退行性变
泛素
脊髓和延髓肌萎缩
雄激素受体
细胞生物学
黑腹果蝇
施耐德2号电池
分子生物学
生物化学
遗传学
基因
RNA干扰
内科学
核糖核酸
医学
癌症
疾病
前列腺癌
作者
Ho Yin Edwin Chan,John M. Warrick,Isabella F M Andriola,Diane E. Merry,Nancy M. Bonini
标识
DOI:10.1093/hmg/11.23.2895
摘要
Spinal and bulbar muscular atrophy (SBMA) is a heritable neurodegenerative disease caused by the expansion of a polyglutamine [poly(Q)] repeat within the androgen receptor (AR) protein. We studied SBMA in Drosophila using an N-terminal fragment of the human AR protein. Expression of a pathogenic AR protein with an expanded poly(Q) repeat in Drosophila results in nuclear and cytoplasmic inclusion formation, and cellular degeneration, preferentially in neuronal tissues. We have studied the influence of ubiquitin-dependent modification and the proteasome pathway on neural degeneration and AR protein fragment solubility. Compromising the ubiquitin/proteasome pathway enhances degeneration and decreases poly(Q) protein solubility. Our data further suggest that Hsp70 and the proteasome act in an additive manner to modulate neurodegeneration. Through the over-expression of a mutant of the SUMO-1 activating enzyme Uba2, we further show that poly(Q)-induced degeneration is intensified when the cellular SUMO-1 protein conjugation pathway is altered. These data suggest that post-translational protein modification, including the ubiquitin/proteasome and the SUMO-1 pathways, modulate poly(Q) pathogenesis.
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