Differential functions of the KRAS splice variants.
Differential functions of the KRAS splice variants.
复制标题
KRAS剪接变体的差异功能。
DOI：
10.1042/bst20221347
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发表时间：
2023-06-28
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
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作者：
RAS蛋白是一种小的gtpase，它将信号从膜受体转导到调节生长和分化的信号通路。4种RAS蛋白由HRAS、KRAS、NRAS三个基因编码。其中，KRAS在人类癌症中发生突变的频率高于其他致癌基因。KRAS前mrna可选择性剪接产生两个转录本，KRAS4A和KRAS4B，它们编码不同的原癌蛋白，这些原癌蛋白几乎完全不同于控制亚细胞运输和膜结合的c端高变区（HVRs）。KRAS4A亚型在4.75亿年前出现在有颌脊椎动物中，并一直存在于所有脊椎动物中，这强烈表明剪接变体的功能不重叠。由于KRAS4B在大多数组织中表达水平较高，因此它被认为是KRAS的主要亚型。然而，关于KRAS4A在肿瘤中的表达以及剪接变异特异性相互作用和功能的新证据引发了人们对该基因产物的兴趣。在这些发现中，kras4a特异性调节己糖激酶I是一个明显的例子。这篇小型综述的目的是提供KRAS的两个剪接变体的起源和不同功能的概述。
RAS proteins are small GTPases that transduce signals from membrane receptors to signaling pathways that regulate growth and differentiation. Four RAS proteins are encoded by three genes — HRAS, KRAS, NRAS. Among them, KRAS is mutated in human cancer more frequently than any other oncogene. The KRAS pre-mRNA is alternatively spliced to generate two transcripts, KRAS4A and KRAS4B, that encode distinct proto-oncoproteins that differ almost exclusively in their C-terminal hypervariable regions (HVRs) that controls subcellular trafficking and membrane association. The KRAS4A isoform arose 475 million years ago in jawed vertebrates and has persisted in all vertebrates ever since, strongly suggesting non-overlapping functions of the splice variants. Because KRAS4B is expressed at higher levels in most tissues, it has been considered the principal KRAS isoform. However, emerging evidence for KRAS4A expression in tumors and splice variant–specific interactions and functions have sparked interest in this gene product. Among these findings, the KRAS4A-specific regulation of hexokinase I is a stark example. The aim of this mini-review is to provide an overview of the origin and differential functions of the two splice variants of KRAS.
影响因子：
30.8
作者：
To, Minh D.;Wong, Christine E.;Karnezis, Anthony N.;Del Rosario, Reyno;Di Lauro, Roberto;Balmain, Allan
通讯作者：
Balmain, Allan