Jul-Larsen Asne, Grudic Amra, Bjerkvig Rolf, Bøe Stig Ove
Department of Biomedicine, University of Bergen, Bergen, Norway.
J Cell Sci. 2009 Apr 15;122(Pt 8):1201-10. doi: 10.1242/jcs.040840.
Nucleoporins and the promyelocytic leukemia protein (PML) represent structural entities of nuclear pore complexes and PML nuclear bodies, respectively. In addition, these proteins might function in a common biological mechanism, because at least two different nucleoporins, Nup98 and Nup214, as well as PML, can become aberrantly expressed as oncogenic fusion proteins in acute myeloid leukemia (AML) cells. Here we show that PML and nucleoporins become directed to common cytoplasmic compartments during the mitosis-to-G1 transition of the cell cycle. These protein assemblies, which we have termed CyPNs (cytoplasmic assemblies of PML and nucleoporins), move on the microtubular network and become stably connected to the nuclear membrane once contact with the nucleus has been made. The ability of PML to target CyPNs depends on its nuclear localization signal, and loss of PML causes an increase in cytoplasmic-bound versus nuclear-membrane-bound nucleoporins. CyPNs are also targeted by the acute promyelocytic leukemia (APL) fusion protein PML-RARalpha and can be readily detected within the APL cell line NB4. These results provide insight into a dynamic pool of cytoplasmic nucleoporins that form a complex with the tumor suppressor protein PML during the G1 phase of the cell cycle.
核孔蛋白和早幼粒细胞白血病蛋白（PML）分别代表核孔复合体和PML核体的结构实体。此外，这些蛋白质可能在一种共同的生物学机制中发挥作用，因为在急性髓系白血病（AML）细胞中，至少两种不同的核孔蛋白Nup98和Nup214以及PML可异常表达为致癌融合蛋白。在此我们表明，在细胞周期的有丝分裂到G1期过渡期间，PML和核孔蛋白被导向共同的细胞质区室。这些蛋白质组装体，我们称之为CyPNs（PML和核孔蛋白的细胞质组装体），在微管网络上移动，一旦与细胞核接触，就会与核膜稳定连接。PML靶向CyPNs的能力取决于其核定位信号，PML的缺失会导致与核膜结合的核孔蛋白相比，细胞质结合的核孔蛋白增加。CyPNs也被急性早幼粒细胞白血病（APL）融合蛋白PML-RARα靶向，并且在APL细胞系NB4中很容易检测到。这些结果为细胞周期G1期期间与肿瘤抑制蛋白PML形成复合物的细胞质核孔蛋白动态池提供了见解。
