Brandt D W, Bruns M E, Bruns D E, Ferguson J E, Burton D W, Deftos L J
Department of Medicine, University of California, San Diego.
Biochem Biophys Res Commun. 1992 Dec 15;189(2):938-43. doi: 10.1016/0006-291x(92)92294-8.
Parathyroid hormone-related protein (PTHrP) is an oncofetal protein that is widely expressed in mammalian tissues. The PTHrP gene is a complex with three transcriptional start-sites, two TATA boxes and a GC-rich region, and three predicted polypeptide products, PTHrP 1-141, PTHrP 1-139, and PTHrP 1-173. The originally discovered form of PTHrP, PTHrP 1-141, and the classical TATA box promoters are generally assumed to be the major pathways of PTHrP gene expression. We have used the polymerase chain reaction (PCR) to study PTHrP gene expression in the human amnion. Our studies demonstrate that the GC-rich promoter is preferentially used and that PTHrP 1-139 is the major PTHrP mRNA expressed in human amnion. PTHrP 1-139 lacks the carboxy-terminal arginine and histidine residues of PTHrP 1-141; these two basic amino acids could have significant effects on the biological activity of PTHrP. These preferential pathways for PTHrP gene expression are shared by malignant and normal human tissues.
甲状旁腺激素相关蛋白(PTHrP)是一种癌胚蛋白,在哺乳动物组织中广泛表达。PTHrP基因是一个具有三个转录起始位点、两个TATA盒和一个富含GC区域的复合体,有三种预测的多肽产物,即PTHrP 1-141、PTHrP 1-139和PTHrP 1-173。最初发现的PTHrP形式PTHrP 1-141以及经典的TATA盒启动子通常被认为是PTHrP基因表达的主要途径。我们利用聚合酶链反应(PCR)研究了人羊膜中PTHrP基因的表达。我们的研究表明,富含GC的启动子被优先使用,且PTHrP 1-139是人羊膜中表达的主要PTHrP mRNA。PTHrP 1-139缺乏PTHrP 1-141的羧基末端精氨酸和组氨酸残基;这两个碱性氨基酸可能对PTHrP的生物学活性有显著影响。PTHrP基因表达的这些优先途径在恶性和正常人体组织中是共有的。