人类新基因的分离和鉴定研究
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摘要
细胞周期调节是细胞重要而又复杂的生命现象之一，在众多与调节有关的环节中，任何一个环节发生问题将导致细胞分裂异常并最终影响到机体的正常功能。CDK蛋白激酶和周期素是目前研究较多的与细胞周期调节有关的一些重要蛋白因子，以它们为核心的调节途径在G2-M过渡期内起关键性作用。新的研究发现在Asperxillus nidulans中，除了p34(CDC2)和cyclin B外还有另外的途径与它一起在G2-M过渡期内共同发挥作用，这就是以NIMA为代表的一些Ser／Thr蛋白激酶所参与的调节途径。NIMA相关的蛋白在大多数的物种中都存在，并形成了一个庞大而又保守的基因家族，在高等哺乳类中，这一家族甚至还衍生出另一类大的家族，即nek或nrk基因家族。近年来的研究成果证实nek基因同样与G2-M过渡期有关，而且nek基因的异常功能可能导致包括PKD在内的多种严重疾病。
为了进一步从人体中分离到nek家族中的其他基因，本研究根据NIMA家族的保守性特点，先从人胎盘cDNA文库中PCR分离到一个探针，再利用该探针筛选人胎盘cDNA文库，最终成功克隆到一个与nimA相关的基因，即NEK6基因。它的完整开放阅读框可能编码一个由306个氨基酸组成的蛋白质。经过Genbank数据库中的查新结果证实，NEK6基因是一个迄今为止尚未报道过的新基因，Genbank登录号为AF087909。在催化功能区，它与小鼠NEK1蛋白具有39.32％的同源性。在大多数的组织中(结肠组织除外)，NEK6基因都能表达一个长1.6kb的mRNA片段，卵巢组织中的NEK6基因表达水平明显高于睾丸组织。应用Radiation Hybrid染色体定位技术，NEK6基因被定位于9号染色体9q33.3-43.11上。结果初步显示：NEK6基因是哺乳类NEK基因家族中的重要成员之一，可能具有Ser／Thr蛋白激酶活性，并在细胞分裂中发挥调节作用。
此外，GMP还原酶是GMP向IMP转变的一个重要的代谢酶，它的功能
Cell cycle regulation is one of the most important and complicated life phenomena for all cells. The cell division will become deviant and the normal function of animals will be affected abnomally as soon as there are some problems on the stages of cell cycle regulation. As some cell cycle factors which had been studied by most researchers, CDK protein kinases and cyclins are the core proteins in a regulating pathway to function mainly during the G2-M transition of cell division. The newly studies showed that some other Ser/Thr protein kinases sampled by NIMA (encoded by nimA of Aspergillus. nidulans) have the same functions as CDK protein kinases and cyclins do. A conservative nimA gene family was found in most organisms and a conservative nek family in advanced mammalias was obvious. The neks genes may functioned in the G2-M transition and some serious diseases including PKD will caused while it's knocked out in the rats.
In order to clone other human members of nek family, we gained a probe from human placenta cDNA library by PCR. A novel gene (i.e NEK6) has been isolated at last by using this probe to screen the human placeta cDNA library. This gene's complete ORF encodes a protein, which is composed with 306 animo acids. The results of gene and protein sequences' Blastzing in the GeneBank data testified that NEK6 was an unreported gene. Its assession number is AF087909 Its functional part in N terminal has 39.32% identity with mouse NEK1 's. In most tissues (except colon tissue), NEK6 gene expressed a 1.6kb transcript and much more in ovary tissue than in testis tissue. NEK6 gene was laterly mapped to the chromosome 9q33.3-43.11 by Radiation Hybrid mapping. These primary results show that NEK6 is a true member of nek gene family and it may function as an enzyme just like the Ser/Thr protein kinases in the cell division regulation.
为了进一步从人体中分离到nek家族中的其他基因，本研究根据NIMA家族的保守性特点，先从人胎盘cDNA文库中PCR分离到一个探针，再利用该探针筛选人胎盘cDNA文库，最终成功克隆到一个与nimA相关的基因，即NEK6基因。它的完整开放阅读框可能编码一个由306个氨基酸组成的蛋白质。经过Genbank数据库中的查新结果证实，NEK6基因是一个迄今为止尚未报道过的新基因，Genbank登录号为AF087909。在催化功能区，它与小鼠NEK1蛋白具有39.32％的同源性。在大多数的组织中(结肠组织除外)，NEK6基因都能表达一个长1.6kb的mRNA片段，卵巢组织中的NEK6基因表达水平明显高于睾丸组织。应用Radiation Hybrid染色体定位技术，NEK6基因被定位于9号染色体9q33.3-43.11上。结果初步显示：NEK6基因是哺乳类NEK基因家族中的重要成员之一，可能具有Ser／Thr蛋白激酶活性，并在细胞分裂中发挥调节作用。
此外，GMP还原酶是GMP向IMP转变的一个重要的代谢酶，它的功能
Cell cycle regulation is one of the most important and complicated life phenomena for all cells. The cell division will become deviant and the normal function of animals will be affected abnomally as soon as there are some problems on the stages of cell cycle regulation. As some cell cycle factors which had been studied by most researchers, CDK protein kinases and cyclins are the core proteins in a regulating pathway to function mainly during the G2-M transition of cell division. The newly studies showed that some other Ser/Thr protein kinases sampled by NIMA (encoded by nimA of Aspergillus. nidulans) have the same functions as CDK protein kinases and cyclins do. A conservative nimA gene family was found in most organisms and a conservative nek family in advanced mammalias was obvious. The neks genes may functioned in the G2-M transition and some serious diseases including PKD will caused while it's knocked out in the rats.
In order to clone other human members of nek family, we gained a probe from human placenta cDNA library by PCR. A novel gene (i.e NEK6) has been isolated at last by using this probe to screen the human placeta cDNA library. This gene's complete ORF encodes a protein, which is composed with 306 animo acids. The results of gene and protein sequences' Blastzing in the GeneBank data testified that NEK6 was an unreported gene. Its assession number is AF087909 Its functional part in N terminal has 39.32% identity with mouse NEK1 's. In most tissues (except colon tissue), NEK6 gene expressed a 1.6kb transcript and much more in ovary tissue than in testis tissue. NEK6 gene was laterly mapped to the chromosome 9q33.3-43.11 by Radiation Hybrid mapping. These primary results show that NEK6 is a true member of nek gene family and it may function as an enzyme just like the Ser/Thr protein kinases in the cell division regulation.
引文
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