PBK/TOPK: A Therapeutic Target Worthy of Attention.
PBK/TOPK: A Therapeutic Target Worthy of Attention.
复制标题
PBK/TOPK：值得关注的治疗靶点
作者：
Han Z;Li L;Huang Y;Zhao H;Luo Y
越来越多的证据表明，PDZ结合激酶（PBK）/T淋巴细胞因子激活的杀伤细胞起源蛋白激酶（TOPK）在有丝分裂活跃细胞，尤其是增殖性恶性细胞的有丝分裂和细胞周期进程中发挥作用。已证实PBK/TOPK与恶性肿瘤的发生、发展及转移相关。因此，它是癌症治疗中的一个潜在治疗靶点。已有诸多研究致力于探索强效PBK/TOPK抑制剂的临床适用性。然而，研究显示PBK/TOPK在正常增殖细胞中也会过度表达，这些细胞包括精子、成人大脑脑室下区的神经前体细胞，此外，在诸如心脏、大脑和肾脏等缺血组织这类病理条件下，PBK/TOPK同样过度表达，并且在细胞增殖和自我更新等生理功能中发挥重要作用。因此，在考虑将PBK/TOPK抑制剂应用于临床实践之前，有必要开展更多研究以加深我们对其的理解。在本研究中，我们首先回顾与有丝分裂和细胞周期调控相关的研究成果、一般特征及信号传导机制。接着，我们回顾PBK/TOPK在包括肿瘤以及心脏、大脑和肾脏缺血等病理条件下的功能。最后，我们总结强效及选择性抑制剂的研究进展，并阐述PBK/TOPK抑制剂在临床应用中的潜在价值。
Accumulating evidence supports the role of PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies. Therefore, it is a potential therapeutic target in cancer therapy. Many studies have been conducted to explore the clinical applicability of potent PBK/TOPK inhibitors. However, PBK/TOPK has also been shown to be overexpressed in normal proliferative cells, including sperm and neural precursor cells in the subventricular zone of the adult brain, as well as under pathological conditions, such as ischemic tissues, including the heart, brain, and kidney, and plays important roles in their physiological functions, including proliferation and self-renewal. Thus, more research is warranted to further our understanding of PBK/TOPK inhibitors before we can consider their applicability in clinical practice. In this study, we first review the findings, general features, and signaling mechanisms involved in the regulation of mitosis and cell cycle. We then review the functions of PBK/TOPK in pathological conditions, including tumors and ischemic conditions in the heart, brain, and kidney. Finally, we summarize the advances in potent and selective inhibitors and describe the potential use of PBK/TOPK inhibitors in clinical settings.
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影响因子：
5.7
作者：
Gao G;Zhang T;Wang Q;Reddy K;Chen H;Yao K;Wang K;Roh E;Zykova T;Ma W;Ryu J;Curiel-Lewandrowski C;Alberts D;Dickinson SE;Bode AM;Xing Y;Dong Z
通讯作者：
Dong Z
影响因子：
2.5
作者：
Fujibuchi, T;Abe, Y;Kito, K
通讯作者：
Kito, K
DOI：
10.1073/pnas.090102397
发表时间：
2000-05-09
影响因子：
11.1
作者：
Gaudet, S;Branton, D;Lue, RA
通讯作者：
Lue, RA
影响因子：
8
作者：
Hu, F.;Gartenhaus, R. B.;Rapoport, A. P.
通讯作者：
Rapoport, A. P.
影响因子：
9.7
作者：
Gao, Tiantao;Hu, Quanfang;Yu, Luoting
通讯作者：
Yu, Luoting