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Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression

Oncogene volume 24, pages 1272–1276 (2005)Cite this article

Abstract

Parafibromin is the 531-amino-acid protein product encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal dominant hyperparathyroidism–jaw tumor familial cancer syndrome, sporadic parathyroid cancer, and a minority of families with isolated hyperparathyroidism. Parafibromin contains no identified functional domains but bears sequence homology to Cdc73p, a budding yeast protein component of the RNA polymerase II-associated Paf1 complex. This study addressed the expression and functional properties of human parafibromin. A survey of human and mouse tissues analysed with polyclonal antibodies to parafibromin showed specific immunoreactivity in adrenal and parathyroid glands, kidney, heart, and skeletal muscle. Subcellular fractionation and laser confocal microscopy of normal human parathyroid gland demonstrated expression of parafibromin in both the cytoplasmic and nuclear compartments. Parafibromin was expressed in four parathyroid adenomas but was absent from two parathyroid carcinomas. Transient overexpression of wild-type parafibromin, but not its Leu64Pro missense mutant implicated in parathyroid cancer and familial isolated hyperparathyroidism, inhibited cell proliferation, and blocked expression of cyclin D1, a key cell cycle regulator previously implicated in parathyroid neoplasia. These results demonstrate that human parafibromin is a nucleocytoplasmic protein with functions consistent with its postulated role as a tumor suppressor protein.

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Acknowledgements

We thank the clinical fellows, Craig Cochran, and the nursing staff of the Clinical Center 8-West patient care unit, our colleagues Dr Monica Skarulis, Lee S Weinstein, and Allen M Spiegel of the NIDDK, and our surgical oncology colleagues Drs Steven K Libutti, James Pingpank, H Richard Alexander and Dao Nguyen of the NCI for their support.

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  1. Metabolic Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA

    Geoffrey E Woodard, Ling Lin, Jian-Hua Zhang, Sunita K Agarwal, Stephen J Marx & William F Simonds

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  1. Geoffrey E Woodard
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Correspondence to William F Simonds.

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Woodard, G., Lin, L., Zhang, JH. et al. Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene 24, 1272–1276 (2005). https://doi.org/10.1038/sj.onc.1208274

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