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Small Changes Huge Impact: The Role of Protein Posttranslational Modifications in Cellular Homeostasis and Disease

机译:微小变化巨大影响:蛋白质翻译后修饰在细胞稳态和疾病中的作用

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摘要

Posttranslational modifications (PTMs) modulate protein function in most eukaryotes and have a ubiquitous role in diverse range of cellular functions. Identification, characterization, and mapping of these modifications to specific amino acid residues on proteins are critical towards understanding their functional significance in a biological context. The interpretation of proteome data obtained from the high-throughput methods cannot be deciphered unambiguously without a priori knowledge of protein modifications. An in-depth understanding of protein PTMs is important not only for gaining a perception of a wide array of cellular functions but also towards developing drug therapies for many life-threatening diseases like cancer and neurodegenerative disorders. Many of the protein modifications like ubiquitination play a decisive role in various drug response(s) and eventually in disease prognosis. Thus, many commonly observed PTMs are routinely tracked as disease markers while many others are used as molecular targets for developing target-specific therapies. In this paper, we summarize some of the major, well-studied protein alterations and highlight their importance in various chronic diseases and normal development. In addition, other promising minor modifications such as SUMOylation, observed to impact cellular dynamics as well as disease pathology, are mentioned briefly.
机译:翻译后修饰(PTM)调节大多数真核生物中的蛋白质功能,并在多种细胞功能中普遍存在。这些修饰对蛋白质上特定氨基酸残基的鉴定,表征和作图对于理解其在生物学环境中的功能意义至关重要。没有蛋白质修饰的先验知识,就不能明确地解读从高通量方法获得的蛋白质组数据的解释。对蛋白质PTM的深入理解不仅对于获得广泛的细胞功能的认识很重要,而且对于开发许多威胁生命的疾病(如癌症和神经退行性疾病)的药物疗法也很重要。许多蛋白质修饰(如泛素化)在各种药物反应中起决定性作用,并最终在疾病预后中起决定性作用。因此,通常将许多常见的PTM作为疾病标记物进行跟踪,而将许多其他PTM用作开发靶标特异性疗法的分子靶标。在本文中,我们总结了一些主要的,经过充分研究的蛋白质改变,并强调了它们在各种慢性疾病和正常发育中的重要性。此外,简要提到了其他有希望的微小修饰,例如SUMOylation,观察到会影响细胞动力学以及疾病病理。

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