Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, Germany.
First Department of Medicine, UKSH, Campus Lübeck, 23538 Lübeck, Germany.
Cells. 2019 Jan 4;8(1):21. doi: 10.3390/cells8010021.
RAC1B is an alternatively spliced isoform of the monomeric GTPase RAC1. It differs from RAC1 by a 19 amino acid in frame insertion, termed exon 3b, resulting in an accelerated GDP/GTP-exchange and an impaired GTP-hydrolysis. Although RAC1B has been ascribed several protumorigenic functions such as cell cycle progression and apoptosis resistance, its role in malignant transformation, and other functions driving tumor progression like epithelial-mesenchymal transition, migration/invasion and metastasis are less clear. Insertion of exon 3b endows RAC1B with specific biochemical properties that, when compared to RAC1, encompass both loss-of-functions and gain-of-functions with respect to the type of upstream activators, downstream targets, and binding partners. In its extreme, this may result in RAC1B and RAC1 acting in an antagonistic fashion in regulating a specific cellular response with RAC1B behaving as an endogenous inhibitor of RAC1. In this review, we strive to provide the reader with a comprehensive overview, rather than critical discussions, on various aspects of RAC1B biology in eukaryotic cells.
RAC1B 是单体 GTP 酶 RAC1 的一种选择性剪接异构体。它通过框内插入 19 个氨基酸与 RAC1 不同，称为外显子 3b，导致 GDP/GTP 交换加速和 GTP 水解受损。尽管 RAC1B 被赋予了几种促进肿瘤发生的功能，如细胞周期进展和抗细胞凋亡，但它在恶性转化中的作用以及其他驱动肿瘤进展的功能，如上皮-间充质转化、迁移/侵袭和转移，尚不明确。外显子 3b 的插入赋予了 RAC1B 特定的生化特性，与 RAC1 相比，这些特性包括上游激活剂、下游靶标和结合伙伴的类型的功能丧失和功能获得。在极端情况下，这可能导致 RAC1B 和 RAC1 以拮抗方式调节特定的细胞反应，RAC1B 作为 RAC1 的内源性抑制剂。在这篇综述中，我们努力为读者提供一个全面的概述，而不是对真核细胞中 RAC1B 生物学的各个方面进行批判性讨论。
