Historical Perspective and Evolutionary Origins of Parathyroid Hormone-Related Protein

Abstract After the discovery of parathyroid hormone-related protein (PTHrP) as the cause of the hypercalcemia of malignancy, it was found to be distributed widely in tissues, with its actions driving many physiologic and pathologic conditions. Its involvement in cancer extended to a contribution to the ability of cancer cells to promote bone resorption and establish as metastases. It was found to have multiple activities within the sequence, including a nuclear localizing sequence and a specific nuclear transport system. PTHrP and parathyroid hormone (PTH) appear to have arisen from a common ancestral gene and the comparative endocrinology and genomics studies focused on finding where the two genes appeared. PTHrP has been identified in bony and cartilaginous fish in the same tissues as in humans, indicating that PTHrP has fundamental and basic physiological roles in all vertebrates. PTHrP has been localized in fish neoplasms suggesting that PTHrP’s role in tumor formation is a conserved role from at least fish to humans. Interestingly, PTH has been identified in both bony and cartilaginous fish even though they lack a parathyroid gland and indicate that PTH’s evolutionary history is much longer too. So the point where PTHrP and PTH were duplicated is still unknown. A comparison among the analogous human, mouse, chicken, xenopus, and fugu sequences of the PTHrP gene demonstrates elements of conservation. When coupled with human Encode data and knowledg...
Source: Clinical Reviews in Bone and Mineral Metabolism - Category: Internal Medicine Source Type: research