磷酸肌醇 3-激酶 (PI3K) 负责磷酸化磷酸肌醇，生成对于调节各种细胞过程（包括细胞生长、存活和代谢）至关重要的次级信号分子。 PI3K 是一种异二聚酶复合物，由催化亚基（p110α、p110β 或 p110δ）和调节亚基（p85）组成。调节亚基 p85 与催化亚基 p110 的结合形成 PI3K 酶的组成部分。 PIK3R1（磷酸肌醇 3 激酶调节亚基 1）属于 PI3K 家族的 IA 类。 PIK3R1 由于选择性剪接而表现出结构复杂性，产生不同的亚型，尤其是 p85α 和 p55α。虽然主要的 p85α 同种型包含多个结构域，包括 Src 同源 3 (SH3) 结构域、断点簇区域同源 (BH) 结构域和 Src 同源 2 (SH2) 结构域（iSH2 和 nSH2），但较短的同种型 p55α 缺乏某些特定的结构域。 p85α 中存在的结构域。在这篇综述中，我们将重点介绍控制 PI3K 信号传导的复杂调控机制以及 PIK3R1 改变对细胞过程的影响。我们将进一步深入研究 PIK3R1 突变在各种癌症类型中的临床意义及其对预后和治疗结果的影响。此外，我们将讨论旨在调节 PI3K 相关通路的靶向治疗的不断发展。总体而言，本综述将深入了解 PIK3R1 在癌症中的动态相互作用，促进精准医学的进步和针对性干预措施的开发。版权所有 © 2024。由 Elsevier Ltd 出版。

Phosphoinositide 3-kinase (PI3K) is responsible for phosphorylating phosphoinositides to generate secondary signaling molecules crucial for regulating various cellular processes, including cell growth, survival, and metabolism. The PI3K is a heterodimeric enzyme complex comprising of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85). The binding of the regulatory subunit, p85, with the catalytic subunit, p110, forms an integral component of the PI3K enzyme. PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) belongs to class IA of the PI3K family. PIK3R1 exhibits structural complexity due to alternative splicing, giving rise to distinct isoforms, prominently p85α and p55α. While the primary p85α isoform comprises multiple domains, including Src homology 3 (SH3) domains, a Breakpoint Cluster Region Homology (BH) domain, and Src homology 2 (SH2) domains (iSH2 and nSH2), the shorter isoform, p55α, lacks certain domains present in p85α. In this review, we will highlight the intricate regulatory mechanisms governing PI3K signaling along with the impact of PIK3R1 alterations on cellular processes. We will further delve into the clinical significance of PIK3R1 mutations in various cancer types and their implications for prognosis and treatment outcomes. Additionally, we will discuss the evolving landscape of targeted therapies aimed at modulating PI3K-associated pathways. Overall, this review will provide insights into the dynamic interplay of PIK3R1 in cancer, fostering advancements in precision medicine and the development of targeted interventions.Copyright © 2024. Published by Elsevier Ltd.