副甲状腺機能亢進症 : 顎腫瘍症候群の原因遺伝子産物パラフィブロミン

Primary hyperparathyroidism is characterized by the calcium-insensitive hypersecretion of parathyroid hormone and formation of parathyroid tumors. The disease usually results from a single parathyroid adenoma, but in a minority of cases is a part of hereditary syndromes; multiple endocrine neoplasia types 1 and 2A, familial isolated hyperparathyroidism, and hyperparathyroidism-jaw tumor (HPT-JT) syndrome. HPT-JT syndrome is characterized by parathyroid tumors, fibro-osseous lesions of the mandible and maxilla, and renal cysts and tumors. The gene whose inactivation is directly associated with the pathogenesis of HPT-JT syndrome has been identified as the tumor suppressor gene HRPT2. Parafibromin, a 531-amino acid protein encoded by HRPT2, has partial homology with the yeast Cdc73, a component of the RNA polymerase II-associated Paf1 complex including Paf1, Leo1, Ctr9, and Rtf1. Parafibromin binds to RNA polymerase II as a part of human Paf1 complex together with human orthologs of Paf1, Leo1, Ctr9. Human Paf1 complex appears to be involved in transcription elongation. Parafibromin has antiproliferative activity by inhibition of cyclin D1 and c-myc proto-oncoprotein. Whereas, we recently demonstrated that parafibromin acts as a positive regulator of cell growth like an oncoprotein in the presence of SV40 large T antigen, indicating parafibroimin has potentially ambivalent functions in tumorigenesis. This review focuses on the functions of parafibromin and human Paf1 complex, providing an insight into its potential involvement in the development of cancer.