A nuclear pore complex‐associated regulation of SUMOylation in meiosis
A nuclear pore complex‐associated regulation of SUMOylation in meiosis
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减数分裂中 SUMO 化的核孔复合体相关调控
DOI：
10.1111/gtc.13003
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发表时间：
2022
期刊：
影响因子：
2.1
通讯作者：
Hiraoka Yasushi
中科院分区：
文献类型：
--
作者：
Yang Hui‐Ju;Asakawa Haruhiko;Li Fu‐An;Haraguchi Tokuko;Shih Hsiu‐Ming;Hiraoka Yasushi
核孔复合体（NPC）在核质和细胞质之间提供了一个可渗透的屏障。在裂殖酵母裂殖酵母中调节减数分裂的NPC成分的一个子集中，我们发现核孔蛋白Nup 132（人类Nup 133的同源物）缺乏导致减数分裂I期间核蛋白的瞬时泄漏，如在nup 132基因缺失突变体中观察到的那样。核蛋白泄漏伴随着小泛素样修饰物（SUMO）特异性泛素样蛋白酶1（Ulp 1）从NPC中释放。Ulp 1保留在核孔防止核蛋白泄漏，并恢复正常减数分裂的突变体缺乏Nup 132。此外，使用质谱分析，我们确定DNA拓扑异构酶2（Top2）和RCC 1相关蛋白（Pim 1）为SUMO化的靶蛋白。在缺少Nup 132的减数分裂细胞中，Top2和Pim 1的SUMO化水平发生改变。高度SUMO化的Top2增加了nup 132基因缺失的减数分裂细胞的着丝粒结合亲和力。Top2 - 12 KR类小泛素化突变体较少定位于着丝粒区域。我们的研究结果表明，染色质结合蛋白的SUMO化受NPC结合的SUMO特异性蛋白酶的调节，对减数分裂的进展很重要。
The nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeastSchizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in thenup132gene‐deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin‐like modifier (SUMO)‐specific ubiquitin‐like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1‐related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres ofnup132gene‐deleted meiotic cells. The Top2‐12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin‐binding proteins is regulated by the NPC‐bound SUMO‐specific protease and is important for the progression of meiosis.