A novel 40kDa N-terminal truncated carboxypeptidase E splice variant: cloning, cDNA sequence analysis and role in regulation of metastatic genes in human cancers

Q2 Biochemistry, Genetics and Molecular Biology
Xuyu Yang, H. Lou, Ya-Ting Chen, Shui-Feng Huang, Y. Loh
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引用次数: 7

Abstract

Carboxypeptidase E (CPE), a prohormone processing enzyme, is a 476- amino acid protein with a signal peptide in its N-terminus and is expressed in the nervous and the endocrine systems. Recent evidence indicate CPE plays various non-enzymatic roles in the endocrine and nervous systems and in various cancers. Besides wild type (WT) CPE, a 40-kDa CPE protein that localizes in the nucleus and cytoplasm has been described in embryonic mouse brain. In this study we have cloned this CPE variant encoding the 40kDa CPE-ΔN protein from human cancer cells. RACE assay and sequence analysis confirmed existence of this CPE variant mRNA, which has 198 nucleotides removed within the first exon and 589 nucleotides from the 3’-UTR, respectively, compared to WT-CPE mRNA. Bioinformatic analysis revealed that this CPE variant mRNA has a shortened open reading frame, which starts coding from the 3rd ATG relative to WT-CPE mRNA and encodes a 40kDa N-terminus truncated CPE protein. RT-PCR and Western blot analysis showed that 40kDa CPE-ΔN is expressed in multiple cancer cell lines and tumor tissues. Overexpression of this 40kDa CPE-ΔN variant up-regulated expression of multiple metastatic genes encompassing different signaling pathways, suggesting potentially an important role of CPE-ΔN in tumor metastasis.
一个新的40kDa n端截断羧基肽酶E剪接变异:克隆、cDNA序列分析及其在人类癌症转移基因调控中的作用
羧基肽酶E (Carboxypeptidase E, CPE)是一种含有476个氨基酸的蛋白,其n端含有一个信号肽,在神经系统和内分泌系统中表达。最近的证据表明,CPE在内分泌和神经系统以及各种癌症中发挥多种非酶作用。除了野生型(WT) CPE外,在胚胎小鼠脑中还发现了一种定位于细胞核和细胞质中的40 kda CPE蛋白。在这项研究中,我们从人类癌细胞中克隆了编码40kDa CPE-ΔN蛋白的CPE变体。RACE实验和序列分析证实了该CPE变异mRNA的存在,与WT-CPE mRNA相比,该变异mRNA在第一个外显子内和3 ' -UTR中分别有198个核苷酸和589个核苷酸被删除。生物信息学分析表明,该CPE变异mRNA具有较短的开放阅读框,相对于WT-CPE mRNA从第3 ATG开始编码,编码40kDa的n端截断CPE蛋白。RT-PCR和Western blot分析显示,40kDa CPE-ΔN在多种癌细胞系和肿瘤组织中均有表达。这种40kDa CPE-ΔN变体的过表达上调了包含不同信号通路的多个转移基因的表达,表明CPE-ΔN在肿瘤转移中可能发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes and Cancer
Genes and Cancer Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
6
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