The SUMO protease SENP6 is a direct regulator of PML nuclear bodies.
The SUMO protease SENP6 is a direct regulator of PML nuclear bodies.
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DOI：
10.1091/mbc.e10-06-0504
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Hay RT
中科院分区：
文献类型：
--
作者：
Hattersley N;Shen L;Jaffray EG;Hay RT
我们发现sumo特异性蛋白酶SENP6可以切割混合的SUMO-1和SUMO-2/3链。SENP6的缺失导致早幼粒细胞白血病（PML）核体中SUMO-2/3和SUMO-1偶联物的积累。SENP6失活导致其在PML核体sumo -2/3富集的核心积聚。生化分析表明sumo修饰的PML是SENP6底物。早幼粒细胞白血病蛋白（PML）是早幼粒细胞核小体（PML NBs）的核心成分。小泛素样修饰剂（SUMO）系统（特别是PML的SUMO化）是PML NBs形成和调控的关键组成部分。SUMO蛋白酶SENP6先前已被证明对SUMO-2/3修饰的底物具有特异性，并表现出对SUMO聚合物的偏好。在这里，我们进一步研究了SENP6的底物特异性，并表明它也能够切割SUMO-1和SUMO-2/3的混合链。SENP6的缺失导致内源性SUMO-2/3和SUMO-1偶联物的积累，免疫荧光分析显示SUMO和PML在PML NBs数量增加中积累。虽然SENP6耗竭会急剧增加PML NBs的大小，但身体的组织结构不受影响。SENP6的催化半胱氨酸突变导致其在PML NBs中积累，生化分析表明sumo修饰的PML是SENP6的底物。
We show that SUMO-specific protease SENP6 can cleave mixed SUMO-1 and SUMO-2/3 chains. Depletion of SENP6 results in accumulation of SUMO-2/3 and SUMO-1 conjugates in promyelocytic leukemia (PML) nuclear bodies. Inactivation of SENP6 results in its accumulation at the SUMO-2/3-rich core of PML nuclear bodies. Biochemical analysis indicates that SUMO-modified PML is a SENP6 substrate. Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3–modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6.