Endo Akinori, Kitamura Naomi, Komada Masayuki
Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Department of Biological Sciences, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
J Biol Chem. 2009 Oct 9;284(41):27918-27923. doi: 10.1074/jbc.M109.037218. Epub 2009 Aug 13.
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.
核仁是一个具有多种细胞功能的亚核区室，包括核糖体生物合成。USP36是一种去泛素化酶，定位于核仁，在调节该细胞器的结构和功能中起重要作用。然而，USP36的定位是如何被调控的仍不清楚。在此，我们鉴定出一段位于USP36 C末端区域的短链碱性氨基酸（RGKEKKIKKFKREKRR），它作为该蛋白的核仁定位信号。我们发现这个基序与核仁磷酸蛋白/B23的一个中央酸性区域相互作用，核仁磷酸蛋白/B23是一种参与多种核仁功能的主要核仁蛋白。敲低核仁磷酸蛋白/B23导致核仁中USP36的量显著减少，而不影响细胞内USP36水平。这与核仁中USP36底物蛋白纤维原蛋白的泛素化水平升高有关。我们得出结论，核仁磷酸蛋白/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。
