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B1.12：一种与 EBV 癌蛋白 LMP1 的细胞外环相互作用的新型肽。

B1.12: a novel peptide interacting with the extracellular loop of the EBV oncoprotein LMP1.

机构信息

Center of Biotechnology of Sfax, Laboratory: Molecular Biotechnology of Eukaryotes, University of Sfax, Sfax, Tunisia.

BVBGR-LR 11ES31, ISBST, University of Manouba, Biotechnopole Sidi Thabet, 2020, Ariana, Tunisia.

出版信息

Sci Rep. 2019 Mar 13;9(1):4389. doi: 10.1038/s41598-019-39732-y.

DOI:10.1038/s41598-019-39732-y
PMID:30867462
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6416395/
Abstract

Latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) plays an important role in EBV-induced cell transformation. Down-regulation of the LMP1 expression had shown promising results on cancer cell therapy. In this study, we identified by Phage display a novel peptide called B1.12 (ACPLDLRSPCG) which selectively binds to the extracellular loop (B1) of the LMP1 oncoprotein as demonstrated by molecular docking, NMR and ITC. Using an LMP1 expressing cell line, we showed that B1.12 decreased cell viability, and induced G0/G1 cell cycle arrest. In addition, the expression of A20, pAkt, and pNFkb (pRelA536) in C666-1 cells treated with B1.12 decreased compared to the untreated cells. In conclusion, we selected a novel peptide able to bind specifically to the extracellular loop of LMP1 and thus modulate its oncogenic properties.

摘要

潜伏膜蛋白 1（LMP1）由 Epstein-Barr 病毒（EBV）编码，在 EBV 诱导的细胞转化中发挥重要作用。下调 LMP1 的表达已在癌细胞治疗方面显示出良好的效果。在这项研究中，我们通过噬菌体展示技术鉴定了一种新型肽，称为 B1.12（ACPLDLRSPCG），它可以特异性地结合到 LMP1 癌蛋白的细胞外环（B1），这一点通过分子对接、NMR 和 ITC 得到了证明。使用表达 LMP1 的细胞系，我们发现 B1.12 降低了细胞活力，并诱导 G0/G1 细胞周期停滞。此外，与未处理的细胞相比，用 B1.12 处理的 C666-1 细胞中 A20、pAkt 和 pNFkb（pRelA536）的表达下降。总之，我们选择了一种能够特异性结合到 LMP1 细胞外环的新型肽，从而调节其致癌特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/b6a4b07bc6fd/41598_2019_39732_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/90e4ac7fdcd5/41598_2019_39732_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/3499a36fa4a2/41598_2019_39732_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/ce0f5eaa883e/41598_2019_39732_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/a7c0a2d23733/41598_2019_39732_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/e05abba8f511/41598_2019_39732_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/2130061a080d/41598_2019_39732_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/ed92082c34c6/41598_2019_39732_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/7818834aedd1/41598_2019_39732_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/b6a4b07bc6fd/41598_2019_39732_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/90e4ac7fdcd5/41598_2019_39732_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/3499a36fa4a2/41598_2019_39732_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/ce0f5eaa883e/41598_2019_39732_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/a7c0a2d23733/41598_2019_39732_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/e05abba8f511/41598_2019_39732_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/2130061a080d/41598_2019_39732_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/ed92082c34c6/41598_2019_39732_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/7818834aedd1/41598_2019_39732_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8257/6416395/b6a4b07bc6fd/41598_2019_39732_Fig9_HTML.jpg

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