Role of NDP kinase in cell growth and differentiation

由于NDP激酶被认为是一种管家酶，因此它可能参与了细胞的生长和分化。事实上，NDP激酶与DNA聚合酶和核糖核苷酸还原酶的相互作用，以及与生长相关的酶活性的增加，在裂殖酵母、粘菌盘基菌、小鼠和人类细胞中都有报道。在本研究中，当我们研究了编码NDP激酶的酿酒酵母YNK基因的过度表达或中断的后果时，生长速度和孢子形成等表型行为没有受到影响。因此，虽然一些证据表明NDP激酶似乎在细胞生长和分化中发挥重要作用，但它们的确切作用尚不清楚。在利用大鼠来源的培养细胞系研究NDP激酶在细胞增殖中的作用的过程中，我们意识到，静止培养细胞系的NDP激酶活性似乎普遍高于正常大鼠组织的提取物。因此，我们询问NDP激酶活性是否与细胞无限生长(永生化)的能力有关，并平行检测了四种人类正常二倍体成纤维细胞及其相应永生化细胞提取物中的NDP激酶活性以及翻译和转录产物。在永生化细胞系中，酶活性持续升高。这一增加与翻译和转录产物的增加有关。此外，两种异构体都被发现增加。

Since NDP kinase is considered to be a housekeeping enzyme, its possible involvement in cell growth and differentiation has been suggested. In fact, interactions of NDP kinase with DNA polymerase and ribonucleotide reductase, and growth associated increase in the enzyme activity in fission yeast Schizosaccharomyces pombe, slime mold Dictyostelium discoideum, mouse and human cells have been documented. In the present study, when we investigated the consequence of overexpression or disruption of a Saccharomyces cerevisiae YNK gene that encodes NDP kinase, phenotypic behaviors such as growth rate and spore formation were unaffected. Therefore, although several lines of evidence suggest that NDP kinases seem to play important role in cell growth and differentiation, their precise role remains unknown.During the course of studies on the role of NDP kinase in cell prolifiration using cultured cell lines of rat origin, we realized that NDP kinase activities in the extracts from resting cultured cell lines seemed generally higher than those from normal rat tissues. Therefore, we asked whether NDP kinase activity is related to the ability of infinite cell growth (immortalization), and examined NDP kinase activity in parallel with translation and transcription products in the extracts from four human normal diploid fibroblasts and their corresponding immortalized cells. The enzyme activity was consistently increased in the immortalized cell lines. This increase was associated with increased translation and transcription products. Further, both isoforms were found to be increased.