Poly (ADP-ribose) polymerase 1 is required for protein localization to Cajal body.
Poly (ADP-ribose) polymerase 1 is required for protein localization to Cajal body.
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DOI：
10.1371/journal.pgen.1000387
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发表时间：
2009-02
期刊：
影响因子：
4.5
通讯作者：
Tulin, Alexei V.
中科院分区：
文献类型：
--
作者：
Kotova, Elena;Jarnik, Michael;Tulin, Alexei V.
最近，被称为聚（ADP-核糖）聚合酶1（PARP 1）的核蛋白被证明在调节许多基因的转录和控制核亚细胞器核仁中起关键作用。已知PARP 1酶催化ADP-核糖转移至多种核蛋白。然而，目前，虽然我们知道体内pADPr的主要受体是PARP 1蛋白本身，但通过PARP 1自修饰，PARP 1自修饰对体内过程的意义尚不清楚。因此，我们研究了PARP 1自身ADP-核糖基化在发育过程中动态核过程中的作用。具体而言，我们发现PARP 1自身修饰是通过体内蛋白质与pADPr的非共价相互作用将关键蛋白质穿梭到Cajal体（CB）中所必需的。我们假设PARP 1蛋白穿梭遵循一系列事件，首先，大多数未修饰的PARP 1蛋白分子与染色质结合并在核仁中积累，然后，第二，在与聚（ADP-核糖）自修饰后，PARP 1与许多核蛋白非共价相互作用，使得所得的蛋白质-pADPr复合物从染色质解离成CB。先前的研究揭示了多聚（ADP-核糖）聚合酶（PARP）蛋白在发育程序调节以及染色质松动和转录激活中的重要作用。我们对PARP蛋白在发育过程中作用的理解的主要差距涉及将PARP蛋白的生物活性整合到核蛋白动力学和基因表达的一般网络中。在这里，我们报告的PARP蛋白活性与蛋白质运输通过卡哈尔体的功能协会。Cajal小体（CB）是调节RNA-蛋白质复合物生物合成的核细胞器，参与转录和剪接。我们证明了（1）PARP存在于CB中，（2）其丢失导致CB分解，（3）PARP水平的增加导致CB的形成，最后，（4）PARP定位是蜕皮激素敏感的。我们进一步提出了一个模型，其中PARP控制蛋白质运输通过CB和CB的形成。
Recently, the nuclear protein known as Poly (ADP-ribose) Polymerase1 (PARP1) was shown to play a key role in regulating transcription of a number of genes and controlling the nuclear sub-organelle nucleolus. PARP1 enzyme is known to catalyze the transfer of ADP-ribose to a variety of nuclear proteins. At present, however, while we do know that the main acceptor for pADPr in vivo is PARP1 protein itself, by PARP1 automodification, the significance of PARP1 automodification for in vivo processes is not clear. Therefore, we investigated the roles of PARP1 auto ADP-ribosylation in dynamic nuclear processes during development. Specifically, we discovered that PARP1 automodification is required for shuttling key proteins into Cajal body (CB) by protein non-covalent interaction with pADPr in vivo. We hypothesize that PARP1 protein shuttling follows a chain of events whereby, first, most unmodified PARP1 protein molecules bind to chromatin and accumulate in nucleoli, but then, second, upon automodification with poly(ADP-ribose), PARP1 interacts non-covalently with a number of nuclear proteins such that the resulting protein-pADPr complex dissociates from chromatin into CB. Previous studies revealed vital roles for the Poly(ADP-ribose) Polymerase (PARP) protein in developmental program regulation, as well as in chromatin loosening and transcriptional activation. The main gap in our understanding of PARP protein roles during development involves integrating the biological activities of PARP protein into a general network of nuclear protein dynamics and gene expression. Here, we report the functional association of PARP protein activity with proteins trafficking through Cajal bodies. Cajal bodies (CBs) are nuclear organelles that regulate the biogenesis of RNA-protein complexes involved in transcription and splicing. We demonstrate that (1) PARP is present in CBs, (2) its loss leads to CB disassembly, (3) an increase in PARP levels leads to formation of CBs, and, finally, (4) PARP localization is ecdysone sensitive. We further propose a model in which PARP controls protein trafficking through the CB and contributes to CB formation.
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DOI：
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发表时间：
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期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
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作者：
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发表时间：
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影响因子：
11.1
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10.1073/pnas.2237114100
发表时间：
2004-01-06
影响因子：
11.1
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