KAP1 is a Novel Substrate for the Arginine Methyltransferase PRMT5.
KAP1 is a Novel Substrate for the Arginine Methyltransferase PRMT5.
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DOI：
10.3390/biology4010041
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发表时间：
2015-01-09
期刊：
影响因子：
4.2
通讯作者：
Cesaro E
中科院分区：
文献类型：
--
作者：
di Caprio R;Ciano M;Montano G;Costanzo P;Cesaro E
Kruppel-associated protein 1 （KAP1）是Kruppel-associated box zinc finger protein （krabb - zfps）的转录辅助抑制因子，可经历多种翻译后修饰，涉及KAP1多种生物学功能的微调。在之前的文章中，我们分析了krabb - zfp家族成员ZNF224介导的kap1依赖性转录抑制分子机制，并确定了蛋白精氨酸甲基转移酶PRMT5是ZNF224抑制复合体的一个组成部分。我们证明了prmt5介导的组蛋白精氨酸甲基化是引发ZNF224转录抑制所必需的。在这项研究中，我们发现KAP1与PRMT5相互作用，是PRMT5甲基化的新底物。此外，我们提供的证据表明，KAP1精氨酸残基的甲基化调节KAP1- znf224的相互作用，从而表明KAP1的翻译后修饰可能积极参与调节znf224介导的抑制。
KRAB-associated protein 1 (KAP1), the transcriptional corepressor of Kruppel-associated box zinc finger proteins (KRAB-ZFPs), is subjected to multiple post-translational modifications that are involved in fine-tuning of the multiple biological functions of KAP1. In previous papers, we analyzed the KAP1-dependent molecular mechanism of transcriptional repression mediated by ZNF224, a member of the KRAB-ZFP family, and identified the protein arginine methyltransferase PRMT5 as a component of the ZNF224 repression complex. We demonstrated that PRMT5-mediated histone arginine methylation is required to elicit ZNF224 transcriptional repression. In this study, we show that KAP1 interacts with PRMT5 and is a novel substrate for PRMT5 methylation. Also, we present evidence that the methylation of KAP1 arginine residues regulate the KAP1-ZNF224 interaction, thus suggesting that this KAP1 post-translational modification could actively contribute to the regulation of ZNF224-mediated repression.