Nucleophosmin/B23 Regulates Ubiquitin Dynamics in Nucleoli by Recruiting Deubiquitylating Enzyme USP36
Nucleophosmin/B23 Regulates Ubiquitin Dynamics in Nucleoli by Recruiting Deubiquitylating Enzyme USP36
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DOI：
10.1074/jbc.m109.037218
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发表时间：
2009-10-09
影响因子：
4.8
通讯作者：
Komada, Masayuki
中科院分区：
文献类型：
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作者：
Endo, Akinori;Kitamura, Naomi;Komada, Masayuki
核仁是具有多种细胞功能的亚核区室，包括核糖体生物发生。 USP36 是一种去泛素化酶，定位于核仁，在调节细胞器的结构和功能中发挥重要作用。然而，USP36 的本地化是如何调控的仍然未知。在这里，我们鉴定了一小段碱性氨基酸 (RGKEKKIKKFKREKRR)，它位于 USP36 的 C 末端区域，并充当该蛋白质的核仁定位信号。我们发现该基序与核磷蛋白/B23（参与各种核仁功能的主要核仁蛋白）的中心酸性区域相互作用。核磷蛋白/B23 的敲低导致核仁中 USP36 的量显着减少，而不影响细胞 USP36 水平。这与纤维蛋白（核仁中的 USP36 底物蛋白）泛素化水平升高有关。我们得出结论，核磷蛋白/B23 将 USP36 招募到核仁，从而作为通过泛素化/去泛素化调节核仁蛋白功能的平台。
The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 is a deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure and function of the organelle. However, how the localization of USP36 is regulated remains unknown. Here, we identified a short stretch of basic amino acids (RGKEKKIKKFKREKRR) that resides in the C-terminal region of USP36 and serves as a nucleolar localization signal for the protein. We found that this motif interacts with a central acidic region of nucleophosmin/B23, a major nucleolar protein involved in various nucleolar functions. Knockdown of nucleophosmin/B23 resulted in a significant reduction in the amount of USP36 in nucleoli, without affecting the cellular USP36 level. This was associated with elevated ubiquitylation levels of fibrillarin, a USP36 substrate protein in nucleoli. We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation.