Emslie E A, Jones T A, Sheer D, Keyse S M
ICRF Molecular Pharmacology Unit, Ninewells Hospital, Dundee, UK.
Hum Genet. 1994 May;93(5):513-6. doi: 10.1007/BF00202814.
Expression of the human CL100 gene is induced in skin fibroblasts in response to oxidative/heat stress and growth factors. The CL100 gene encodes a dual specificity (Tyr/Thr) protein phosphatase that specifically inactivates mitogen-activated protein (MAP) kinase in vitro. In addition, CL100 is able to suppress the activation of MAP kinase by oncogenic ras in extracts of Xenopus oocytes. Thus, the CL100 phosphatase may play an important role in the negative regulation of cellular proliferation and is a likely candidate for a tumour-suppressor gene. Here, we show that DNA sequences homologous to CL100 are present in genomic DNA isolated from mouse, chicken, Xenopus and Drosophila, indicating that the CL100 gene is highly conserved. Using an assay based on the polymerase chain reaction, in conjunction with genomic DNA obtained from human-rodent somatic-cell hybrids, we have determined that the CL100 gene is situated on chromosome 5. Fluorescence in situ hybridisation using a CL100 genomic probe confirms that the CL100 mRNA is transcribed from a single genetic locus and maps the gene to 5q34.
人类CL100基因的表达在皮肤成纤维细胞中因氧化/热应激和生长因子而被诱导。CL100基因编码一种双特异性(酪氨酸/苏氨酸)蛋白磷酸酶,该酶在体外能特异性地使丝裂原活化蛋白(MAP)激酶失活。此外,CL100能够在非洲爪蟾卵母细胞提取物中抑制致癌性ras对MAP激酶的激活。因此,CL100磷酸酶可能在细胞增殖的负调控中起重要作用,并且很可能是肿瘤抑制基因的候选者。在此,我们表明从小鼠、鸡、非洲爪蟾和果蝇分离的基因组DNA中存在与CL100同源的DNA序列,这表明CL100基因高度保守。使用基于聚合酶链反应的分析方法,并结合从人 - 啮齿动物体细胞杂种获得的基因组DNA,我们确定CL100基因位于5号染色体上。使用CL100基因组探针进行荧光原位杂交证实CL100 mRNA从单个基因位点转录,并将该基因定位到5q34。