SUMOylation regulates Lem2 function in centromere clustering and silencing

SUMOylation regulates Lem2 function in centromere clustering and silencing
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SUMOylation 调节 Lem2 在着丝粒聚类和沉默中的功能

DOI:
10.1101/2022.11.02.514898
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发表时间:
2022
期刊:
--
影响因子:
--
通讯作者:
Strachan J
Strachan J
中科院分区:
--
文献类型:
--
作者:
Strachan J

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小修饰素SUMO的调节在很大程度上依赖于介导SUMO在底物蛋白上的附着和去除的酶的空间控制。在这里,我们表明,在裂殖酵母裂殖酵母,SUMO蛋白酶Ulp 1从核膜的离域的结果在着丝粒缺陷,可以归因于超SUMO化在核周边。出乎意料的是,我们发现,虽然这种局部的超SUMO化损害着丝粒沉默,它也可以增强着丝粒聚类。此外,这两种作用至少部分依赖于内核膜蛋白Lem 2的SUMO化。Lem 2以前曾参与多种生物过程,包括促进着丝粒聚集和沉默,但这些不同的活动是如何协调的尚不清楚;我们的观察表明,SUMO化作为一种调节开关,调节Lem 2与竞争伙伴蛋白的相互作用,以平衡其在替代途径中的作用。我们的研究结果还揭示了SUMO化在促进着丝粒聚集中的一个以前未被重视的作用。
Regulation by the small modifier SUMO is heavily dependent on spatial control of enzymes that mediate the attachment and removal of SUMO on substrate proteins. Here, we show that in the fission yeast Schizosaccharomyces pombe, delocalisation of the SUMO protease Ulp1 from the nuclear envelope results in centromeric defects that can be attributed to hyper-SUMOylation at the nuclear periphery. Unexpectedly, we find that although this localised hyper-SUMOylation impairs centromeric silencing, it can also enhance centromere clustering. Moreover, both effects are at least partially dependent on SUMOylation of the inner nuclear membrane protein Lem2. Lem2 has previously been implicated in diverse biological processes, including the promotion of both centromere clustering and silencing, but how these distinct activities are coordinated was unclear; our observations suggest a model whereby SUMOylation serves as a regulatory switch, modulating Lem2 interactions with competing partner proteins to balance its roles in alternative pathways. Our findings also reveal a previously unappreciated role for SUMOylation in promoting centromere clustering.
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