Fucosylated Proteome Profiling Identifies a Fucosylated, Non-Ribosomal, Stress-Responsive Species of Ribosomal Protein S3.
Fucosylated Proteome Profiling Identifies a Fucosylated, Non-Ribosomal, Stress-Responsive Species of Ribosomal Protein S3.
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作者：
Watson G;Lester D;Ren H;Forsyth CM;Medina E;Gonzalez Perez D;Darville L;Yao J;Luca V;Koomen J;Cen L;Lau E
岩藻糖基化失调已被表征为几种疾病状态的潜在原因或发病机制的贡献者。然而，迄今为止，对于岩藻糖基化如何以及哪些蛋白质、信号通路和细胞过程受到影响还没有清楚的了解。在这里，我们的特点是由岩藻糖结合凝集素识别的蛋白质，并意外地发现，许多细胞内蛋白质是pupelinate受翻译后岩藻糖基化。我们进一步发现，细胞内核糖体蛋白S3的岩藻糖基化响应刺激，它似乎是独立的目前特征的岩藻糖基化途径。这项工作表明，岩藻糖基化对细胞内蛋白质的作用至今未被充分认识，并支持细胞内岩藻糖基化能力的存在，这是不完全知道的。已知编码控制岩藻糖基化的蛋白质的基因的改变在几种发育障碍中起致病作用，例如Dowling-Degos病2和先天性糖基化IIc型障碍（CDGIIc）。最近的研究提供了证据表明，岩藻糖基化的变化可能有助于几种不同类型癌症的发展和进展。因此，重要的是要详细了解岩藻糖基化在疾病状态下是如何改变的，以便为治疗目的开发干预措施。在这份报告中，我们发现岩藻糖基化发生在许多细胞内蛋白质。这是一个有趣的发现，因为岩藻糖基化机制仅限于分泌途径，并且被认为主要影响细胞膜结合和分泌蛋白。我们发现核糖体蛋白S3（RPS 3）在正常组织和癌细胞中是岩藻糖基化的，并且其岩藻糖基化的程度似乎对包括MAPK抑制剂在内的应激有反应，这表明了翻译后蛋白质功能的新作用。我们的数据确定了一种新的核糖体独立的岩藻糖基化RPS 3，与参与RNA转录后调控的蛋白质相互作用，如异质核核糖核蛋白U（HNRNPU），以及与非编码RNA的优势。这些数据突出了RPS 3的新作用，考虑到先前报道的RPS 3的致癌作用，其可能代表在诸如癌症的病理学中受到干扰的功能。总之，我们的研究结果表明岩藻糖基化在直接影响细胞内蛋白质功能中的作用是以前未被认识的。
Dysregulated fucosylation has been characterized as an underlying cause or a contributor to the pathogenesis of several disease states. However, to date, there is not a clear understanding of how and what proteins, signaling pathways, and cellular processes are impacted by fucosylation. Here, we characterized the proteins recognized by a fucose-binding lectin and unexpectedly discovered that many intracellular proteins are putatively subject to posttranslational fucosylation. We further found that fucosylation on intracellular ribosomal protein S3 responds to stimulus, and that it appears to be independent of the currently characterized fucosylation pathway. This work suggests a to-date-underappreciated role for fucosylation on intracellular proteins and supports the existence of fucosylation capabilities within cells that is not fully known. Alterations in genes encoding for proteins that control fucosylation are known to play causative roles in several developmental disorders, such as Dowling-Degos disease 2 and congenital disorder of glycosylation type IIc (CDGIIc). Recent studies have provided evidence that changes in fucosylation can contribute to the development and progression of several different types of cancers. It is therefore important to gain a detailed understanding of how fucosylation is altered in disease states so that interventions may be developed for therapeutic purposes. In this report, we find that fucosylation occurs on many intracellular proteins. This is an interesting finding, as the fucosylation machinery is restricted to the secretory pathway and is thought to predominately affect cell-membrane-bound and secreted proteins. We find that Ribosomal protein S3 (RPS3) is fucosylated in normal tissues and in cancer cells, and that the extent of its fucosylation appears to respond to stress, including MAPK inhibitors, suggesting a new role in posttranslational protein function. Our data identify a new ribosome-independent species of fucosylated RPS3 that interacts with proteins involved in posttranscriptional regulation of RNA, such as Heterogeneous nuclear ribonucleoprotein U (HNRNPU), as well as with a predominance of non-coding RNAs. These data highlight a novel role for RPS3, which, given previously reported oncogenic roles for RPS3, might represent functions that are perturbed in pathologies such as cancer. Together, our findings suggest a previously unrecognized role for fucosylation in directly influencing intracellular protein functions.
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影响因子：
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DOI：
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发表时间：
2009-02-01
影响因子：
5.1
作者：
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DOI：
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影响因子：
3.1
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影响因子：
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