层粘连蛋白病的逆转：SUN1 的奇特案例。
Reversal of laminopathies: the curious case of SUN1.
机构信息
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.
出版信息
Nucleus. 2012 Sep-Oct;3(5):418-21. doi: 10.4161/nucl.21714. Epub 2012 Aug 16.
Abstract
Mutations in the LMNA gene are associated with a spectrum of human dystrophic diseases termed the "nuclear laminopathies." We recently found that the accumulation of the inner nuclear envelope proteins SUN1 is pathogenic in progeric and dystrophic laminopathies. This conclusion arose from the unexpected observation that the deletion of Sun1, instead of accelerating aging, actually ameliorated the progeric and dystrophic phenotypes in Lmna-deficient mice. In human cells, knocking down SUN1 corrected the nuclear aberrancies and the senescent tendencies of HGPS (Hutchinson-Gilford progeria syndrome) skin fibroblasts. Here we offer additional comments on the contributions of SUN1 and the process of normal protein turnover to cellular aging.
摘要
LMNA 基因突变与一系列被称为“核层板病”的人类进行性营养不良疾病有关。我们最近发现，内核膜蛋白 SUN1 的积累在进行性和营养不良性层板病中是致病的。这一结论源于一个意外的观察结果，即 Sun1 的缺失并没有加速衰老，反而实际上改善了 Lmna 缺陷型小鼠的进行性和营养不良表型。在人类细胞中，敲低 SUN1 纠正了 HGPS（Hutchinson-Gilford 早衰综合征）皮肤成纤维细胞的核异常和衰老趋势。在这里，我们对 SUN1 的贡献和正常蛋白质周转过程对细胞衰老的影响提供了更多的评论。
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本文引用的文献
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Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies.核内包膜蛋白 Sun1 的积累与早老性和营养不良性层粘连蛋白病的发病机制有关。
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Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells.雷帕霉素逆转亨廷顿舞蹈病综合征细胞的表型，并增强突变蛋白的清除。
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