.png){kind=icon}
返回
Rare Codons Regulate KRas Oncogenesis
.png){kind=icon}
OA
AI
DOI：10.1016/j.cub.2012.11.031.png)
.png){kind=icon}
.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
Oncogenic mutations in the small Ras GTPases KRas, HRas, and NRas render the proteins constitutively GTP bound and active, a state that promotes cancer [1]. Ras proteins share similar to 85% amino acid identity [2], are activated by [3] and signal through [4] the same proteins, and can exhibit functional redundancy [5, 6]. Nevertheless, manipulating expression or activation of each isoform yields different cellular responses [7-10] and tumorigenic phenotypes [11-13], even when different ras genes are expressed from the same locus [6]. We now report a novel regulatory mechanism hardwired into the very sequence of RAS genes that underlies how such similar proteins impact tumorigenesis differently. Specifically, despite their high sequence similarity, KRAS is poorly translated compared to HRAS due to enrichment in genomically underrepresented or rare codons. Converting rare to common codons increases KRas expression and tumorigenicity to mirror that of HRas. Furthermore, in a genome-wide survey, similar gene pairs with opposing codon bias were identified that not only manifest dichotomous protein expression but also are enriched in key signaling protein classes and pathways. Thus, synonymous nucleotide differences affecting codon usage account for differences between HRas and KRas expression and function and may represent a broader regulation strategy in cell signaling.
Keyword:
HIGH-LEVEL EXPRESSION
MESSENGER-RNAS
K-RAS
GENE
ADULT
NRAS
TRANSFORMATION
PROLIFERATION
CONSEQUENCES
SPECIFICITY
AI总结
对已上传原文的论文进行重点信息的提取，主要内容包括：简要概述、研究摘要、背景介绍、关键亮点、图文解析、展望与总结。
期刊
IF:
7.5
论文数:
2.2W
被引数:
7.8W
机构
引用论文
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists生物信息学富集工具: 通往大型基因列表综合功能分析的路径.png)
NUCLEIC ACIDS RESEARCHOAAI
NUCLEIC ACIDS RESEARCHIF13.1
OAAI分享收藏Experimentally Increased Codon Bias in the Drosophila Adh Gene Leads to an Increase in Larval, But Not Adult, Alcohol Dehydrogenase ActivityGENETICSOAAI
GENETICSIF5.1
OAAI分享收藏A load/line adaptive zero voltage switching DC/DC converter used in electric vehicles一种用于电动汽车的负载/线路自适应零电压开关DC/DC变换器
PREAI
分享收藏
查看更多内容