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Front Mol Biosci. 2024 Aug 9;11:1436976. doi: 10.3389/fmolb.2024.1436976. eCollection 2024.
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Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.异常可变剪接在黑色素瘤中的作用和机制——对靶向治疗和免疫治疗耐药性的影响
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Neuroblastoma RAS viral oncogene homolog mRNA is differentially spliced to give five distinct isoforms: implications for melanoma therapy.神经母细胞瘤 RAS 病毒癌基因同源物 mRNA 经不同剪接可产生五种不同的异构体:对黑色素瘤治疗的启示。
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本文引用的文献

1
Neuroblastoma RAS viral oncogene homolog mRNA is differentially spliced to give five distinct isoforms: implications for melanoma therapy.神经母细胞瘤 RAS 病毒癌基因同源物 mRNA 经不同剪接可产生五种不同的异构体:对黑色素瘤治疗的启示。
Melanoma Res. 2019 Oct;29(5):491-500. doi: 10.1097/CMR.0000000000000623.
2
Cancer statistics, 2015.癌症统计数据,2015 年。
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. doi: 10.3322/caac.21254. Epub 2015 Jan 5.
3
Indications and options for systemic therapy in melanoma.黑色素瘤的系统治疗的适应证和选择。
Surg Clin North Am. 2014 Oct;94(5):1049-58, viii. doi: 10.1016/j.suc.2014.07.007. Epub 2014 Aug 6.
4
NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation.NRAS 异构体差异影响下游通路、细胞生长和细胞转化。
Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4179-84. doi: 10.1073/pnas.1401727111. Epub 2014 Feb 28.
5
Beneficial effects of RAF inhibitor in mutant BRAF splice variant-expressing melanoma.RAF抑制剂对表达突变BRAF剪接变体的黑色素瘤的有益作用。
Mol Cancer Res. 2014 May;12(5):795-802. doi: 10.1158/1541-7786.MCR-13-0581. Epub 2014 Feb 11.
6
Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitors.新一代选择性RAF抑制剂对突变BRAF剪接变体信号传导的抑制作用。
Pigment Cell Melanoma Res. 2014 May;27(3):479-84. doi: 10.1111/pcmr.12218. Epub 2014 Feb 10.
7
PDBStat: a universal restraint converter and restraint analysis software package for protein NMR.PDBStat:一种用于蛋白质 NMR 的通用约束转换器和约束分析软件包。
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8
Helical ambivalency induced by point mutations.由点突变引起的螺旋矛盾性。
BMC Struct Biol. 2013 May 15;13:9. doi: 10.1186/1472-6807-13-9.
9
Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations.BRAF V600 突变型黑色素瘤的联合 BRAF 和 MEK 抑制治疗。
N Engl J Med. 2012 Nov 1;367(18):1694-703. doi: 10.1056/NEJMoa1210093. Epub 2012 Sep 29.
10
BRAFV600E: implications for carcinogenesis and molecular therapy.BRAFV600E:致癌作用和分子治疗的意义。
Mol Cancer Ther. 2011 Mar;10(3):385-94. doi: 10.1158/1535-7163.MCT-10-0799.

NRAS同工型5的结构表征

Structural characterization of NRAS isoform 5.

作者信息

Markowitz Joseph, Mal Tapas K, Yuan Chunhua, Courtney Nicholas B, Patel Mitra, Stiff Andrew R, Blachly James, Walker Christopher, Eisfeld Ann-Kathrin, de la Chapelle Albert, Carson William E

机构信息

Moffitt Cancer Center Department of Cutaneous Oncology, The Ohio State University, Columbus, Ohio.

The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.

出版信息

Protein Sci. 2016 May;25(5):1069-74. doi: 10.1002/pro.2916. Epub 2016 Mar 24.

DOI:10.1002/pro.2916
PMID:26947772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4838646/
Abstract

It was recently discovered that the NRAS isoform 5 (20 amino acids) is expressed in melanoma and results in a more aggressive cell phenotype. This novel isoform is responsible for increased phosphorylation of downstream targets such as AKT, MEK, and ERK as well as increased cellular proliferation. This structure report describes the NMR solution structure of NRAS isoform 5 to be used as a starting point to understand its biophysical interactions. The isoform is highly flexible in aqueous solution, but forms a helix-turn-coil structure in the presence of trifluoroethanol as determined by NMR and CD spectroscopy.

摘要

最近发现NRAS亚型5(20个氨基酸)在黑色素瘤中表达,并导致更具侵袭性的细胞表型。这种新型亚型导致下游靶点如AKT、MEK和ERK的磷酸化增加以及细胞增殖增加。本结构报告描述了NRAS亚型5的核磁共振溶液结构,作为理解其生物物理相互作用的起点。该亚型在水溶液中高度灵活,但通过核磁共振和圆二色光谱法测定,在三氟乙醇存在下形成螺旋-转角-螺旋结构。