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解码聚(RC)结合蛋白1(PCBP1),铁死亡山麓下被低估的守护者。

Decoding poly (RC)-binding protein 1 (PCBP1), the underrated guard at the foothill of ferroptosis.

作者信息

Rithvik Arulkumaran, Wadhavane Sakshi, Rasool Mahaboobkhan

机构信息

Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.

Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632014, India.

出版信息

Pathol Res Pract. 2025 Feb;266:155771. doi: 10.1016/j.prp.2024.155771. Epub 2024 Dec 12.

Abstract

PCBP1 is a multifunctional adaptor protein, whose function as an iron chaperone and epigenetic regulator of several chemical messengers involved in ferroptosis has garnered much attention. Herein, this review, several attempts have been made to simplify our understanding of the complex roles of PCBP1. The review begins by elucidating the relevance of PCBP1 in key events governing ferroptosis. We expeditiously shed light on some of the important mechanisms that have critical implications for the ferroptosis landscape. For instance, senescence, EMT, hypoxia, and regulation of the cell cycle and immune checkpoints, among others, have been demonstrated to influence ferroptosis sensitivity to varying degrees. Thus, this review entails a conscious attempt to carefully examine the relevance of PCBP1 in such potential mechanisms. Furthermore, we investigated the therapeutic relevance of PCBP1 in tumor biology and autoimmunity, while underscoring the contrasting perspective of ferroptosis targeting across the disease spectrum. Finally, we debate the different strategies that can be exploited to target PCBP1 in promoting or inhibiting ferroptosis.

摘要

PCBP1是一种多功能衔接蛋白,其作为铁伴侣以及参与铁死亡的几种化学信使的表观遗传调节剂的功能备受关注。在本综述中,我们进行了多次尝试以简化我们对PCBP1复杂作用的理解。本综述首先阐明了PCBP1在调控铁死亡的关键事件中的相关性。我们迅速揭示了一些对铁死亡格局具有关键影响的重要机制。例如,衰老、上皮-间质转化、缺氧以及细胞周期和免疫检查点的调节等,已被证明在不同程度上影响铁死亡敏感性。因此,本综述有意识地尝试仔细研究PCBP1在这些潜在机制中的相关性。此外,我们研究了PCBP1在肿瘤生物学和自身免疫中的治疗相关性,同时强调了针对不同疾病谱靶向铁死亡的不同观点。最后,我们讨论了在促进或抑制铁死亡过程中可用于靶向PCBP1的不同策略。

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