Isolation of a functional human gene for brain creatine kinase.
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Daouk GH, Kaddurah-Daouk R, Putney S, Kingston R, Schimmel P
Isolation of a functional human gene for brain creatine kinase.
J Biol Chem. 1988 Feb 15;263(5):2442-6.
- PubMed ID
- 2828370 [ View in PubMed]
- Abstract
There is evidence that the gene for the B isozyme of creatine kinase is regulated during cell differentiation, is under hormonal control, and is activated in a small cell lung carcinoma. In order to investigate further the mechanisms of these processes, the human gene was isolated and the structure of the promoter region was determined. A human DNA fragment of 8 kilobase pairs was shown to encompass the entire coding region and 850 base pairs (bp) of the 5'-flanking sequence. This fragment was transfected into three cell lines and shown to express functional enzyme. The 5'-end of the gene is split by a 230-bp intron that is located 12 bp upstream of the initiator ATG codon. Transcription initiation occurs at a site that is approximately 69 bp upstream of the 5'-end of this intron. The DNA sequence in the region upstream of the 5'-end of the mRNA is suggestive of two superimposed promoters that contain additional sequence elements that are known to regulate expression of other eukaryote genes. The 5'-region also has a remarkable homology to the overlapping promoters of the adenovirus EIIaE gene. These elements collectively form the basis for initial investigations of how this gene is controlled.