SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.
SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.
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DOI：
10.1083/jcb.200510103
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发表时间：
2006-09-25
影响因子：
7.8
通讯作者：
Dasso, Mary
中科院分区：
文献类型：
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作者：
Mukhopadhyay, Debaditya;Ayaydin, Ferhan;Kolli, Nagamalleswari;Tan, Shyh-Han;Anan, Tadashi;Kametaka, Ai;Azuma, Yoshiaki;Wilkinson, Keith D;Dasso, Mary
小泛素相关修饰剂 (SUMO) 加工和解偶联由哨兵蛋白特异性蛋白酶/泛素样蛋白酶 (SENP/Ulps) 介导。我们发现 SUMO 特异性蛋白酶 1 (SUSP1) 是一种哺乳动物 SENP/Ulp，定位于核质内。表达增强型绿色荧光蛋白 (EGFP) 与个体 SUMO 旁系同源物融合的细胞系内 SUSP1 的耗尽导致 EGFP-SUMO2 和 -SUMO3 重新分布，特别是进入早幼粒细胞白血病 (PML) 体。进一步的分析表明，这种变化主要是由于 SUMO2/3 解结合活性的缺乏所致。在这种情况下，PML体变大，数量增多。我们没有观察到 EGFP-SUMO1 的类似重新分布。我们使用乙烯基砜抑制剂和模型底物研究了 SUSP1 的特异性。我们发现 SUSP1 对 SUMO2/3 有强烈的旁系同源物偏向，并且它优先作用于含有三个或更多 SUMO2/3 部分的底物。总之，我们的研究结果表明，SUSP1 可能在分解高度缀合的 SUMO2 和 -3 物种方面发挥特殊作用，这对于 PML 身体的维持至关重要。
Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green fluorescent protein (EGFP) fusions to individual SUMO paralogues caused redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia (PML) bodies. Further analysis suggested that this change resulted primarily from a deficit of SUMO2/3-deconjugation activity. Under these circumstances, PML bodies became enlarged and increased in number. We did not observe a comparable redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong paralogue bias toward SUMO2/3 and that it acts preferentially on substrates containing three or more SUMO2/3 moieties. Together, our findings argue that SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3 species that is critical for PML body maintenance.