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核编码人胰岛素原异构体潜在功能的证据。

Evidence for potential functionality of nuclearly-encoded humanin isoforms.

作者信息

Bodzioch Marek, Lapicka-Bodzioch Katarzyna, Zapala Barbara, Kamysz Wojciech, Kiec-Wilk Beata, Dembinska-Kiec Aldona

机构信息

Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Kopernika 15a, 31-501 Krakow, Poland.

出版信息

Genomics. 2009 Oct;94(4):247-56. doi: 10.1016/j.ygeno.2009.05.006. Epub 2009 May 27.

DOI:10.1016/j.ygeno.2009.05.006
PMID:19477263
Abstract

Humanin (HN) is a recently identified neuroprotective and antiapoptotic peptide derived from a portion of the mitochondrial MT-RNR2 gene. We provide bioinformatic and expression data suggesting the existence of 13 MT-RNR2-like nuclear loci predicted to maintain the open reading frames of 15 distinct full-length HN-like peptides. At least ten of these nuclear genes are expressed in human tissues, and respond to staurosporine (STS) and beta-carotene. Sequence comparisons of the nuclear HN isoforms and their homologues in other species reveal two consensus motifs, encompassing residues 5-11 (GFS/NCLLL), and 14-19 (SEIDLP/S). Proline vs serine in position 19 may determine whether the peptide is secreted or not, while threonine in position 13 may be important for cell surface receptor binding. Cytoprotection against the STS-induced apoptosis conferred by the polymorphic HN5 variant, in which threonine in position 13 is replaced with isoleucine, is reduced compared to the wild type HN5 peptide.

摘要

人胰岛素(HN)是一种最近发现的神经保护和抗凋亡肽,源自线粒体MT-RNR2基因的一部分。我们提供的生物信息学和表达数据表明,存在13个预测可维持15种不同全长HN样肽开放阅读框的MT-RNR2样核基因座。这些核基因中至少有十个在人体组织中表达,并对星形孢菌素(STS)和β-胡萝卜素产生反应。核HN异构体及其在其他物种中的同源物的序列比较揭示了两个共有基序,包括第5-11位残基(GFS/NCLLL)和第14-19位残基(SEIDLP/S)。第19位的脯氨酸与丝氨酸可能决定该肽是否分泌,而第13位的苏氨酸可能对细胞表面受体结合很重要。与野生型HN5肽相比,多态性HN5变体(其中第13位的苏氨酸被异亮氨酸取代)对STS诱导的细胞凋亡的细胞保护作用降低。

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