Kim J M, Sato N, Yamada M, Arai K, Masai H
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Biol Chem. 1998 Sep 4;273(36):23248-57. doi: 10.1074/jbc.273.36.23248.
Saccharomyces cerevisiae CDC7 encodes a serine/threonine kinase required for G1/S transition of the yeast cells. We previously reported human and Xenopus cDNAs encoding CDC7-related kinases and suggested the possibility that chromosomal replication of higher eukaryotes may be regulated through conserved mechanisms involving Cdc7-related kinases. Here we report a murine cDNA and gene (muCdc7) encoding a serine/threonine kinase related to CDC7. The predicted coding frame for the longest cDNA for muCdc7 consists of 564 amino acids, which shares 46, 77, and 93% identity, respectively, with those of budding yeast, Xenopus, and human in kinase conserved domains. The chromosomal gene for muCdc7, located at the band 5E5 on the mouse chromosome 5, consists of 12 exons, and its exon/intron organization shares some similarity with that of other protein kinases including Cdk and cAMP-dependent kinase. Transcription of muCdc7, initiated at multiple sites over the 370-base pair promoter region, is repressed in the resting state and is induced at the G1/S boundary after growth factor stimulation in a growth factor-dependent cell line. Transient transfection assays indicated that a 231-base pair segment of the muCdc7 promoter containing three putative E2F binding sites and one Sp1 site but lacking TATA sequence is sufficient for response to growth stimulation.
酿酒酵母CDC7编码一种酵母细胞G1/S期转换所需的丝氨酸/苏氨酸激酶。我们先前报道了编码CDC7相关激酶的人类和非洲爪蟾cDNA,并提出高等真核生物的染色体复制可能通过涉及Cdc7相关激酶的保守机制进行调控的可能性。在此,我们报道了一个编码与CDC7相关的丝氨酸/苏氨酸激酶的小鼠cDNA和基因(muCdc7)。muCdc7最长cDNA的预测编码框由564个氨基酸组成,在激酶保守结构域中,分别与芽殖酵母、非洲爪蟾和人类的编码框具有46%、77%和93%的同一性。muCdc7的染色体基因位于小鼠5号染色体的5E5带,由12个外显子组成,其外显子/内含子组织与包括Cdk和cAMP依赖性激酶在内的其他蛋白激酶有一些相似之处。muCdc7的转录在370碱基对的启动子区域的多个位点起始,在静止状态下受到抑制,在生长因子依赖性细胞系中生长因子刺激后在G1/S边界处被诱导。瞬时转染实验表明,muCdc7启动子的一个231碱基对片段,包含三个假定的E2F结合位点和一个Sp1位点但缺乏TATA序列,足以对生长刺激做出反应。