Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36
Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36
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DOI：
10.1242/jcs.044461
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发表时间：
2009-03-01
影响因子：
4
通讯作者：
Komada, Masayuki
中科院分区：
文献类型：
--
作者：
Endo, Akinori;Matsumoto, Masaki;Komada, Masayuki
核仁是核亚室，是核糖体生物发生的场所。以前的研究表明，蛋白质泛素化与核仁活动有关。在这里，我们展示了USP36，一种功能未知的去泛素化酶，调节哺乳动物细胞中的核仁活动。USP36通过含有碱性氨基酸伸展的C-末端区域定位于核仁。USP36的显性-负性抑制导致核仁中泛素-蛋白质结合物的积累，提示核仁是USP36的作用部位。USP36去泛素化核仁蛋白核磷脂/B23和纤维蛋白，并通过对抗泛素化介导的蛋白酶体降解来稳定它们。RNAi介导的细胞USP36缺失导致rRNA转录和加工水平降低，核仁形态不发达，细胞质核糖体水平略有下降，最终导致细胞增殖率下降。我们的结论是，USP36通过去泛素化核仁底物蛋白，包括核磷蛋白/B23和纤维蛋白，在调节核仁的结构和功能中起着至关重要的作用。
The nucleolus is a subnuclear compartment and the site of ribosome biogenesis. Previous studies have implicated protein ubiquitylation in nucleolar activity. Here we show that USP36, a deubiquitylating enzyme of unknown function, regulates nucleolar activity in mammalian cells. USP36 localized to nucleoli via the C-terminal region, which contains basic amino acid stretches. Dominant-negative inhibition of USP36 caused the accumulation of ubiquitin-protein conjugates in nucleoli, suggesting that nucleoli are the site of USP36 action. USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation. RNAi-mediated depletion of cellular USP36 resulted in reduced levels of rRNA transcription and processing, a less-developed nucleolar morphology and a slight reduction in the cytoplasmic ribosome level, which eventually led to a reduced rate of cell proliferation. We conclude that by deubiquitylating various nucleolar substrate proteins including nucleophosmin/B23 and fibrillarin, USP36 plays a crucial role in regulating the structure and function of nucleoli.