DNA-independent PARP-1 activation by phosphorylated ERK2 increases EIk1 activity: A link to histone acetylation
DNA-independent PARP-1 activation by phosphorylated ERK2 increases EIk1 activity: A link to histone acetylation
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DOI：
10.1016/j.molcel.2006.12.012
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发表时间：
2007-01-26
期刊：
影响因子：
16
通讯作者：
Seger, Rony
中科院分区：
文献类型：
--
作者：
Cohen-Armon, Malka;Visochek, Leonid;Seger, Rony
多聚ADP核糖聚合酶(PARPS)通过多ADP核糖基化催化核蛋白的翻译后修饰。DNA链断裂刺激了丰富的核蛋白PARP-1的催化活性，而PARP-1的激活是启动DNA修复所必需的。在这里，我们表明PARP-1也作用于细胞外信号调节激酶(ERK)信号级联，介导生长和分化。这些发现揭示了PARP-11的另一种激活模式，它不涉及与DNA结合或DNA损伤。在无细胞体系中，重组的PARP-11被强烈激活，从而通过与磷酸化的ERK2直接相互作用而聚合ADP核糖化，激活的PARP-1显著增加了ERK2催化的转录因子ELK1的磷酸化。在用神经生长因子处理的皮质神经元和刺激的心肌细胞中，PARP-1的激活促进了ERK诱导的ELK1磷酸化、核心组蛋白乙酰化和ELK1靶基因c-fos的转录。这些发现为PARP-1在ERK信号转导通路中的活性提供了证据。
PolyADP-ribose polymerases (PARPs) catalyze a posttranslational modification of nuclear proteins by polyADP-ribosylation. The catalytic activity of the abundant nuclear protein PARP-1 is stimulated by DNA strand breaks, and PARP-1 activation is required for initiation of DNA repair. Here we show that PARP-1 also acts within extracellular signal-regulated kinase (ERK) signaling cascade that mediates growth and differentiation. The findings reveal an alternative mode of PARP-11 activation, which does not involve binding to DNA or DNA damage. In a cell-free system, recombinant PARP-11 was intensively activated and thereby polyADP-ribosylated by a direct interaction with phosphorylated ERK2, and the activated PARP-1 dramatically increased ERK2-catalyzed phosphorylation of the transcription factor Elk1. In cortical neurons treated with nerve growth factors and in stimulated cardiomyocytes, PARP-1 activation enhanced ERK-induced Elk1-phosphorylation, core histone acetylation, and transcription of the Elk1-target gene c-fos. These findings constitute evidence for PARP-1 activity within the ERK signal-transduction pathway.