Liang Ya-Chen, Lee Chia-Chin, Yao Ya-Li, Lai Chien-Chen, Schmitz M Lienhard, Yang Wen-Ming
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
Sci Rep. 2016 May 23;6:26509. doi: 10.1038/srep26509.
Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells.
早幼粒细胞白血病核体（PML-NBs）是基于PML的核结构，可调节多种细胞过程。小泛素样修饰物（SUMO）共价缀合过程即SUMO化，是PML-NBs形成和破坏所必需的。然而，SUMO化如何调节这些过程的详细机制仍不清楚。在此，我们报告SUMO5，一种新型SUMO变体，介导PML-NBs的生长和破坏。PML在赖氨酸160处的多聚SUMO5缀合促进了PML-NB组分的募集，从而扩大了PML-NBs。SUMO5还增加了PML的多聚SUMO2/3缀合，导致RNF4介导的PML-NBs破坏。急性早幼粒细胞白血病癌蛋白PML-RARα阻断PML的SUMO5缀合，导致PML的细胞质移位和PML-NBs的破坏。我们的工作不仅鉴定了SUMO家族的一个新成员，还揭示了人类细胞中PML-NB生命周期的机制基础。
