Hongqiao Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Digestive Endoscopy Center, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Pharmacol Res. 2020 Jan;151:104546. doi: 10.1016/j.phrs.2019.104546. Epub 2019 Nov 15.
The LIM protein Ajuba contains an unstructured proline/glycine-rich preLIM region in the N terminus and conserved tandem LIM motifs in the C terminus. Additionally, Ajuba contains both nuclear export sequences (NES) and nuclear localization sequences (NLS), which enable Ajuba shuttle between the cytoplasm and the nucleus. Thus, Ajuba can act as a versatile scaffold participating in assembly of variety of protein complexes to execute multiple cellular functions including cell adhesion, motility, mitosis, survival, gene expression, microRNA processing and mechanical force sensing. Numerous studies have demonstrated that Ajuba plays important roles in oncogenesis and progression by regulating major signalling pathways such as Wnt, RAS/ERK, JAK/STAT and Hippo, and by acting as a co-regulator of key transcription factors such as Snail, Sp1 and nuclear hormone receptors. Clinically, Ajuba is highly expressed in various types of tumors and can be a marker for prognosis and diagnosis. In this review, we aim to summarize the up-to-date literatures on the signaling pathways mediated by Ajuba and its associated protein complexes in oncogenesis, and to discuss Ajuba as a potential target for new therapeutics to treat cancers.
LIM 蛋白 Ajuba 在 N 端含有一个无结构的脯氨酸/甘氨酸丰富的 preLIM 区,在 C 端含有保守的串联 LIM 基序。此外,Ajuba 还含有核输出序列 (NES) 和核定位序列 (NLS),这使得 Ajuba 能够在细胞质和细胞核之间穿梭。因此,Ajuba 可以作为一种多功能支架,参与多种蛋白质复合物的组装,执行多种细胞功能,包括细胞黏附、运动、有丝分裂、存活、基因表达、microRNA 处理和机械力感应。大量研究表明,Ajuba 通过调节 Wnt、RAS/ERK、JAK/STAT 和 Hippo 等主要信号通路,以及作为 Snail、Sp1 和核激素受体等关键转录因子的共调节剂,在肿瘤发生和进展中发挥重要作用。临床上,Ajuba 在各种类型的肿瘤中高度表达,可作为预后和诊断的标志物。在这篇综述中,我们旨在总结 Ajuba 及其相关蛋白质复合物在肿瘤发生过程中介导的信号通路的最新文献,并讨论 Ajuba 作为治疗癌症的新疗法的潜在靶点。