Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery

IF 6.7 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kun Ping Lu, Xiao Zhen Zhou
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引用次数: 0

Abstract

Protein phosphorylation is one of the most common mechanisms regulating cellular signaling pathways, and many kinases and phosphatases are proven drug targets. Upon phosphorylation, protein functions can be further regulated by the distinct isomerase Pin1 through cis-trans isomerization. Numerous protein targets and many important roles have now been elucidated for Pin1. However, no tools are available to detect or target cis and trans conformation events in cells. The development of Pin1 inhibitors and stereo- and phospho-specific antibodies has revealed that cis and trans conformations have distinct and often opposing cellular functions. Aberrant conformational changes due to the dysregulation of Pin1 can drive pathogenesis but can be effectively targeted in age-related diseases, including cancers and neurodegenerative disorders. Here, we review advances in understanding the roles of Pin1 signaling in health and disease and highlight conformational regulation as a distinct signal transduction checkpoint in disease development and treatment.
磷酸化后 Pin1 催化的构象调控:细胞信号传导和药物发现中的一个独特检查点
蛋白质磷酸化是调节细胞信号通路的最常见机制之一,许多激酶和磷酸酶已被证明是药物靶点。磷酸化后,不同的异构酶 Pin1 可通过顺反异构进一步调节蛋白质功能。目前已经阐明了 Pin1 的许多蛋白质靶点和重要作用。然而,目前还没有工具可以检测或锁定细胞中的顺式和反式构象事件。Pin1 抑制剂以及立体和磷酸化特异性抗体的开发揭示了顺式和反式构象具有不同的、通常是相反的细胞功能。由于 Pin1 的失调而导致的异常构象变化可以驱动致病机制,但在与年龄相关的疾病(包括癌症和神经退行性疾病)中,可以有效地针对这些疾病进行治疗。在此,我们回顾了在理解 Pin1 信号在健康和疾病中的作用方面取得的进展,并强调构象调节是疾病发展和治疗过程中一个独特的信号转导检查点。
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来源期刊
Science Signaling
Science Signaling BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
9.50
自引率
0.00%
发文量
148
审稿时长
3-8 weeks
期刊介绍: "Science Signaling" is a reputable, peer-reviewed journal dedicated to the exploration of cell communication mechanisms, offering a comprehensive view of the intricate processes that govern cellular regulation. This journal, published weekly online by the American Association for the Advancement of Science (AAAS), is a go-to resource for the latest research in cell signaling and its various facets. The journal's scope encompasses a broad range of topics, including the study of signaling networks, synthetic biology, systems biology, and the application of these findings in drug discovery. It also delves into the computational and modeling aspects of regulatory pathways, providing insights into how cells communicate and respond to their environment. In addition to publishing full-length articles that report on groundbreaking research, "Science Signaling" also features reviews that synthesize current knowledge in the field, focus articles that highlight specific areas of interest, and editor-written highlights that draw attention to particularly significant studies. This mix of content ensures that the journal serves as a valuable resource for both researchers and professionals looking to stay abreast of the latest advancements in cell communication science.
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