Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy
Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy
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DOI：
10.1093/hmg/ddq231
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发表时间：
2010-08-15
影响因子：
3.5
通讯作者：
Monteiro, Mervyn J.
中科院分区：
文献类型：
--
作者：
Rothenberg, Cara;Srinivasan, Deepa;Monteiro, Mervyn J.
自噬是溶酶体中细胞器和部分细胞质被降解的过程。已知有几种不同形式的自噬，主要通过将货物运送到溶酶体进行降解的方式来区分。泛素最近被报道调节巨型自噬，这是一种自噬形式，胞液中的货物被包装在双层膜结构中或自噬小体中，自噬小体与溶酶体融合以进行降解。在这里，我们用不同的形态和生化方法证实，泛素存在于HeLa细胞的自噬小体以及小鼠的脑和肝组织中。免疫共沉淀研究表明，泛喹啉与自噬标记Lc3结合在一个复合体中，泛素表达的减少减少了自噬小体的形成，这与Lc3-I成熟为Lc3-II形式的蛋白质的减少有关。我们发现，泛素在巨自噬和伴侣介导的自噬(CMA)过程中都被降解，后者涉及蛋白质主动运输到溶酶体内。我们讨论了这种退化在调节宏自噬和CMA之间的串扰中的意义。最后，我们证明了泛素保护细胞免受饥饿诱导的细胞死亡，这些细胞死亡是通过过表达突变的阿尔茨海默病PS2N141I蛋白和含有74种多谷氨酸的绿色荧光蛋白(GFP)-Huntingtin外显子-1融合蛋白来实现的。
Autophagy is the process by which organelles and portions of the cytoplasm are degraded in lysosomes. Several different forms of autophagy are known that are distinguishable chiefly by the mode in which cargo is delivered to the lysosome for degradation. Ubiquilin was recently reported to regulate macroautophagy, the form of autophagy in which cytosolic cargo is packaged in a double-membrane structure or autophagosome that fuses with lysosomes for degradation. We confirm here using different morphological and biochemical procedures that ubiquilin is present in autophagosomes in HeLa cells and in brain and liver tissue of mouse. Coimmunoprecipitation studies indicated that ubiquilin binds the autophagosome marker LC3 in a complex and that reduction of ubiquilin expression reduces autophagosome formation, which correlates with a reduction in maturation of LC3-I to the LC3-II form of the protein. We found that ubiquilin is degraded during both macroautophagy and during chaperone-mediated autophagy (CMA), the latter of which involves the active transport of proteins into lysosomes. We discuss the implication of this degradation in mediating cross-talk between macroautophagy and CMA. Finally, we demonstrate that ubiquilin protects cells against starvation-induced cell death propagated by overexpression of mutant Alzheimer's disease PS2N141I protein and green fluorescent protein (GFP)-huntingtin exon-1 fusion protein containing 74 polyglutamines.