C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation
C-terminal motifs in promyelocytic leukemia protein isoforms critically regulate PML nuclear body formation
复制标题
早幼粒细胞白血病蛋白亚型中的 C 端基序关键调节 PML 核体形成
DOI：
10.1242/jcs.202879
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发表时间：
2017-10-15
影响因子：
4
通讯作者：
Tang, Jun
中科院分区：
文献类型：
--
作者：
Li, Chuang;Peng, Qiongfang;Tang, Jun
摘要早幼粒细胞白血病蛋白（PML）核体（NB）是一种亚核蛋白结构，参与多种重要的细胞功能。PML-NB由PML同种型组装，并且小泛素样修饰物（SUMO）与SUMO相互作用基序（SIM）之间的接触在此过程中至关重要。PML同种型含有一个共同的N-末端区域和一个可变的C-末端。然而，C-末端区域对PML-NB形成的贡献仍然不清楚。在这里，使用高分辨率显微镜，我们表明，SIM的突变明显影响由每个单独的PML亚型形成的NB的结构，PML-III和PML-V的变化最小，PML-I和PML-IV显着受损。我们进一步确定了几个C-末端元素，是重要的调节NB结构，并提供了强有力的证据表明，在PML-IV的8b元素具有很强的能力，与SUMO-1和SUMO-2相互作用，并在NB的形成至关重要的参与。我们的研究结果强调了PML C-末端在NB组装和功能中的重要性，并提供了对PML-NB组装的每个独特亚型的分子见解。总结：PML-NB是一种重要的亚核蛋白结构，其形成受每种PML亚型独特的C-末端部分的差异调节。
ABSTRACT Promyelocytic leukemia protein (PML) nuclear bodies (NBs), which are sub-nuclear protein structures, are involved in a variety of important cellular functions. PML-NBs are assembled by PML isoforms, and contact between small ubiquitin-like modifiers (SUMOs) with the SUMO interaction motif (SIM) are critically involved in this process. PML isoforms contain a common N-terminal region and a variable C-terminus. However, the contribution of the C-terminal regions to PML-NB formation remains poorly defined. Here, using high-resolution microscopy, we show that mutation of the SIM distinctively influences the structure of NBs formed by each individual PML isoform, with that of PML-III and PML-V minimally changed, and PML-I and PML-IV dramatically impaired. We further identify several C-terminal elements that are important in regulating NB structure and provide strong evidence to suggest that the 8b element in PML-IV possesses a strong ability to interact with SUMO-1 and SUMO-2, and critically participates in NB formation. Our findings highlight the importance of PML C-termini in NB assembly and function, and provide molecular insight into the PML-NB assembly of each distinctive isoform. Summary: The formation of PML-NBs, important sub-nuclear protein structures, is differentially regulated by the unique C-terminal portion of each PML isoform.