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首页> 外文期刊>Epigenetics & Chromatin >Ubiquitin C-terminal hydrolase isozyme L1 is associated with shelterin complex at interstitial telomeric sites
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Ubiquitin C-terminal hydrolase isozyme L1 is associated with shelterin complex at interstitial telomeric sites

机译:泛素C末端水解酶同工酶L1与间质端粒位点的庇护素复合体相关

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Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells and has been associated with various diseases, including many cancers. It is a multifunctional protein involved in deubiquitination, ubiquitination and ubiquitin homeostasis, but its specific roles are disputed and still generally undetermined. Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage. Chromatin immunoprecipitation and sequencing revealed that UCHL1 localizes to TTAGGG repeats at telomeres and interstitial telomeric sequences, as do TRF1 and TRF2, components of the shelterin complex. A weak or transient interaction between UCHL1 and the shelterin complex was confirmed by immunoprecipitation and proximity ligation assays. UCHL1 and RAP1, also known as TERF2IP and a component of the shelterin complex, were bound to the nuclear scaffold. We demonstrated a novel feature of UCHL1 in binding telomeres and interstitial telomeric sites.
机译:泛素C末端水解酶同工酶L1(UCHL1)主要在神经元细胞和神经内分泌细胞中表达,并与包括多种癌症在内的各种疾病有关。它是一种涉及去泛素化,泛素化和泛素体内稳态的多功能蛋白,但其具体作用尚有争议,仍未确定。本文中,我们证明UCHL1与某些前列腺癌细胞系(包括源自脑转移部位的DU 145细胞)以及具有神经元谱系的HEK293T胚胎肾细胞中的基因组DNA相关。染色质的免疫沉淀和测序结果表明,UCHL1定位于端粒和间质端粒序列的TTAGGG重复序列,而TRA1,TRF2则是庇护蛋白复合物的组成部分。免疫沉淀和邻近结扎实验证实了UCHL1与伞菌蛋白复合物之间的弱相互作用或短暂相互作用。 UCHL1和RAP1(也称为TERF2IP)和防护蛋白复合物的一个组成部分与核支架结合。我们展示了端粒和间质端粒结合端粒中的UCHL1的新功能。

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