THE PARATHYROID HORMONE-RELATED PROTEIN GENE AND ITS EXPRESSION

Parathyroid hormone-related protein (PTHrP) was originally identified as a tumor product, but it is now established that PTHrP is expressed in many tissues where it exerts paracrine functions. Three potential isoforms of PTHrP, 139, 141 and 173 amino acids in length, have been described and these isoforms result from alternative splicing of the PTHrP gene. The gene is composed of nine exons of which only two are invariant in PTHrP transcripts. The other seven exons may be represented in the PTHrP mRNA complement as a result of alternative splicing, which allows for the production of up to 15 transcripts. Three spatially-distinct promoters, two TATA and one GC-rich region, are responsible for transcription of the gene and these appear to be differentially regulated. The PTHrP gene contains nucleotide sequence motifs in common with members of the immediate-early response gene family, as well as other hallmark features which include induction by growth factors, serum or cycloheximide and relatively short-lived mRNA.