Fratta P, Engel W K, Van Leeuwen F W, Hol E M, Vattemi G, Askanas V
USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, CA 90017-1912, USA.
Neurology. 2004 Sep 28;63(6):1114-7. doi: 10.1212/01.wnl.0000138574.56908.5d.
Mutant ubiquitin (UBB+1), a product of "molecular misreading," is toxic to cells because its ubiquitinated form inhibits the proteasome, contributing to accumulation of misfolded proteins and their ensuing toxicity. The authors demonstrate in 10 sporadic inclusion body myositis (s-IBM) muscle biopsies that UBB+1 is accumulated in aggregates containing amyloid-beta and phosphorylated-tau. In s-IBM, UBB+1 may be pathogenic by inhibiting proteasome, thereby promoting accumulation of cytotoxic misfolded amyloid-beta and phosphorylated-tau.
突变泛素（UBB+1）是“分子错读”的产物，对细胞有毒性，因为其泛素化形式会抑制蛋白酶体，导致错误折叠蛋白的积累及其随之而来的毒性。作者在10例散发性包涵体肌炎（s-IBM）肌肉活检中发现，UBB+1在含有β淀粉样蛋白和磷酸化tau蛋白的聚集体中积累。在s-IBM中，UBB+1可能通过抑制蛋白酶体而具有致病性，从而促进细胞毒性错误折叠的β淀粉样蛋白和磷酸化tau蛋白的积累。
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