Nek8, a NIMA family kinase member, is overexpressed in primary human breast tumors
Nek8, a NIMA family kinase member, is overexpressed in primary human breast tumors
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DOI：
10.1016/j.gene.2003.12.002
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发表时间：
2004-03-17
期刊：
影响因子：
3.5
通讯作者：
Boylan, JF
中科院分区：
文献类型：
--
作者：
Bowers, AJ;Boylan, JF
人类Nek（NIMA相关激酶）激酶家族目前包含11个成员。我们已经确定Nek 8为Nek激酶家族的新成员。对于许多Nek家族成员，原发性肿瘤表达数据和功能有限。然而，所有的Nek家族蛋白与来自丝状真菌构巢曲霉的Never In MitosisA基因（NIMA）激酶具有相当大的同源性。NIMA及其最密切相关的人类直系同源物Nek 2是G（2）/M进程所必需的，并在有丝分裂期间促进中心体成熟。我们从原代人结肠cDNA文库中分离出Nek 8，发现它与小鼠Nek 8高度同源。最近，一个以前命名的Nek 8序列在Genbank中被重新命名为Nek 9/Nercc 1，因为它与鼠Nek 8缺乏同源性而与鼠Nek 9具有高度同源性。有趣的是，在我们的研究中，系统发育分析表明，人类Nek 8和Nek 9形成Nek家族中的一个亚家族。Nek 8与Nek家族激酶结构域以及染色体凝聚结构域（RCC 1）的调节因子具有高度同源性，所述染色体凝聚结构域（RCC 1）也存在于Nek 9中。人Nek 8的开放阅读框编码692个氨基酸的蛋白质，计算分子量为75 kDa。Nek 8在正常人乳腺组织和乳腺肿瘤之间差异表达。在U2-OS细胞中过表达突变的激酶结构域Nek 8导致肌动蛋白的减少，以及cdk 1/cyclinB 1水平的小幅增加。我们的数据首次证明Nek 8是一个新的肿瘤相关基因，与Nek蛋白激酶家族具有相当大的序列同源性，并可能参与G（2）/M进展。(C)2004 Elsevier B. V.保留所有权利。
The family of human Nek (NIMA Related Kinase) kinases currently contains 11 members. We have identified Nek8 as a new member of the Nek kinase family. For many of the Nek family members, primary tumor expression data and function have been limited. However, all of the Nek family proteins share considerable homology with the Never In Mitosis, gene A (NIMA) kinase from the filamentous fungus Aspergillus nidulans. NIMA, as well as its most closely related human ortholog, Nek2, are required for G(2)/M progression and promote centrosome maturation during mitosis. We isolated Nek8 from a primary human colon cDNA library, and found it to be highly homologous to murine Nek8. Recently, a previously named Nek8 sequence was renamed Nek9/Nercc1 in Genbank due to its lack of homology to murine Nek8 and its high homology to murine Nek9. Interestingly, in our study, phylogenetic analysis suggests that human Nek8 and Nek9 form a subfamily within the Nek family. Nek8 has high homology to the Nek family kinase domain as well as to a regulator of chromosome condensation domain (RCC1), which is also present in Nek9. The open reading frame of human Nek8 encodes a 692 amino-acid protein with a calculated molecular weight of 75 kDa. Nek8 is differentially expressed between normal human breast tissue and breast tumors. Overexpression of a mutated kinase domain Nek8 in U2-OS cells led to a decrease in actin protein, and a small increase in the level of cdk1/ cyclinB1. Our data demonstrate for the first time that Nek8 is a novel tumor associated gene, and shares considerable sequence homology with the Nek family of protein kinases and may be involved in G(2)/M progression. (C) 2004 Elsevier B.V. All rights reserved.