β-transducin repeat-containing protein (β-TrCP), one of the well-characterized F-box proteins, acts as a substrate receptor and constitutes an active SCF^β-TrCP E3 ligase with a scaffold protein CUL1, a RING protein RBX1, and an adaptor protein SKP1. β-TrCP plays a critical role in the regulation of various physiological and pathological processes, including signal transduction, cell cycle progression, cell migration, DNA damage response, and tumorigenesis, by governing burgeoning amounts of key regulators for ubiquitination and proteasomal degradation. Given that a variety of β-TrCP substrates are well-known oncoproteins and tumor suppressors, and dysregulation of β-TrCP is frequently identified in human cancers, β-TrCP plays a vital role in carcinogenesis. In this review, we first briefly introduce the characteristics of β-TrCP1, β-TrCP2, and SCF^β-TrCP ubiquitin ligase, and then discuss SCF^β-TrCP ubiquitin ligase regulated biological processes by targeting its substrates for degradation. Moreover, we summarize the regulation of β-TrCP1 and β-TrCP2 at multiple layers and further discuss the various roles of β-TrCP1 and β-TrCP2 in human cancer, functioning as either an oncoprotein or a tumor suppressor in a manner dependent of cellular context. Finally, we provide novel insights for future perspectives on the potential of targeting β-TrCP1 and β-TrCP2 for cancer therapy.

中文翻译：

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β-TrCP1/2在致癌作用中的特征和作用

含 β-转导蛋白重复序列​​的蛋白质 (β-TrCP) 是一种充分表征的 F-box 蛋白，可作为底物受体并构成活性 SCF ^β-TrCPE3 连接酶与支架蛋白 CUL1、RING 蛋白 RBX1 和接头蛋白 SKP1。β-TrCP 通过控制泛素化和蛋白酶体降解的关键调节因子的迅速增长，在调节各种生理和病理过程中发挥关键作用，包括信号转导、细胞周期进程、细胞迁移、DNA 损伤反应和肿瘤发生。鉴于各种 β-TrCP 底物是众所周知的癌蛋白和肿瘤抑制因子，并且在人类癌症中经常发现 β-TrCP 的失调，β-TrCP 在致癌作用中起着至关重要的作用。在这篇综述中，我们首先简要介绍了 β-TrCP1、β-TrCP2 和 SCF ^β-TrCP泛素连接酶的特性，然后讨论了 SCF ^β-TrCP泛素连接酶通过靶向其降解底物来调节生物过程。此外，我们总结了 β-TrCP1 和 β-TrCP2 的多层调控，并进一步讨论了 β-TrCP1 和 β-TrCP2 在人类癌症中的各种作用，以依赖于细胞的方式作为癌蛋白或肿瘤抑制因子发挥作用。语境。最后，我们为未来靶向 β-TrCP1 和 β-TrCP2 用于癌症治疗的潜力提供了新的见解。