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DOI | 10.1038/s41467-018-03510-7 |
Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer | |
Mitra, Shreya1; Montgomery, Jeffrey E.2,3; Kolar, Matthew J.4,5; Li, Gang2,3; Jeong, Kang J.1; Peng, Bo6; Verdine, Gregory L.4,5; Mills, Gordon B.1; Moellering, Raymond E.2,3 | |
2017-09-22 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Recent evidence has established a role for the small GTPase RAB25, as well as related effector proteins, in enacting both pro-oncogenic and anti-oncogenic phenotypes in specific cellular contexts. Here we report the development of all-hydrocarbon stabilized peptides derived from the RAB-binding FIP-family of proteins to target RAB25. Relative to unmodified peptides, optimized stapled peptides exhibit increased structural stability, binding affinity, cell permeability, and inhibition of RAB25:FIP complex formation. Treatment of cancer cell lines in which RAB25 is pro-oncogenic with an optimized stapled peptide, RFP14, inhibits migration, and proliferation in a RAB25-dependent manner. In contrast, RFP14 treatment augments these phenotypes in breast cancer cells in which RAB25 is tumor suppressive. Transcriptional profiling identified significantly altered transcripts in response to RAB25 expression, and treatment with RFP14 opposes this expression profile. These data validate the first cell-active chemical probes targeting RAB-family proteins and support the role of RAB25 in regulating context-specific oncogenic phenotypes. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000411526700005 |
WOS关键词 | PROMOTE INVASIVE MIGRATION ; CANINE KIDNEY-CELLS ; ALPHA-5-BETA-1 INTEGRIN ; 3D MICROENVIRONMENTS ; TERMINAL DOMAIN ; BREAST-CANCER ; GTPASE ; IDENTIFICATION ; EXPRESSION ; COMPLEX |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203739 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA; 2.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; 3.Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA; 4.Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA; 5.Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA; 6.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA |
推荐引用方式 GB/T 7714 | Mitra, Shreya,Montgomery, Jeffrey E.,Kolar, Matthew J.,et al. Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Mitra, Shreya.,Montgomery, Jeffrey E..,Kolar, Matthew J..,Li, Gang.,Jeong, Kang J..,...&Moellering, Raymond E..(2017).Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer.NATURE COMMUNICATIONS,8. |
MLA | Mitra, Shreya,et al."Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer".NATURE COMMUNICATIONS 8(2017). |
条目包含的文件 | 条目无相关文件。 |
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