Regulation of p53 activity in nuclear bodies by a specific PML isoform
Regulation of p53 activity in nuclear bodies by a specific PML isoform
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DOI：
10.1093/emboj/19.22.6185
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发表时间：
2000-11-15
期刊：
影响因子：
11.4
通讯作者：
Del Sal, G
中科院分区：
文献类型：
--
作者：
Fogal, V;Gostissa, M;Del Sal, G
SUMO - 1对早幼粒细胞白血病蛋白（PML）的共价修饰是核体（NBs）组装的先决条件，核体是在多种人类疾病中被破坏的亚核结构，且与转录和生长控制有关。在此我们证明，p53可通过一种特定的PML异构体（PML3）或通过SUMO - 1和hUbc9的共表达而被招募到核体中，核定位依赖于p53通过其核心结构域与PML3的一个C末端区域的直接结合。p53重新定位到核体中以一种启动子特异性的方式增强p53的反式激活作用并影响细胞存活。我们的结果表明在依赖PML和依赖p53的生长抑制途径之间存在一种相互作用，这意味着核体及其驻留蛋白作为p53功能的调节因子具有重要作用。
Covalent modification of the promyelocytic leukaemia protein (PML) by SUMO-1 is a prerequisite for the assembly of nuclear bodies (NBs), subnuclear structures disrupted in various human diseases and linked to transcriptional and growth control. Here we demonstrate that p53 is recruited into NBs by a specific PML isoform (PML3) or by coexpression of SUMO-1 and hUbc9, NE targeting depends on the direct association of p53, through its core domain, with a C-terminal region of PML3. The relocalization of p53 into NBs enhances p53 transactivation in a promoter-specific manner and affects cell survival. Our results indicate the existence of a cross-talk between PML- and p53-dependent growth suppression pathways, implying an important role for NBs and their resident proteins as modulators of p53 functions.