Nuclear and nucleolar localization of parathyroid hormone-related protein

Parathyroid hormone-related protein (PTHrP) was first discovered as the fac tor causing hypercalcaemia produced by solid tumours frequently associated with the head and neck, breast, lung and kidney. The homology of its amino- terminus to parathyroid hormone (PTH; eight of the first 13 residues are id entical), enables it to share the same receptor and perform similar biologi cal functions to PTH. The sequences of PTHrP C-terminal to its PTH-like reg ion confer functions such as transplacental calcium transport, renal bicarb onate excretion and in vitro osteoclast inhibition. Recent findings have sh own that PTHrP is a nuclear/nucleolar protein in certain tissues and that t his localization is cell cycle-regulated, mediated by the middle portion of the molecule, and involves the nuclear import receptor importin beta 1. Th e present review discusses what is known about the pathway by which PTHrP l ocalizes to the nucleus/nucleolus and the putative roles it may have there.