Synonyms
Historical Background
Knowledge of mammalian CDC73 has essentially been driven by focused efforts to map, and then characterize, a gene responsible for familial primary hyperparathyroidism. Primary hyperparathyroidism (HPT) is estimated to affect three in every 1000 people. Primary HPT refers to hypersecretion of parathyroid hormone (PTH) by chief cells in the parathyroid in a setting of disrupted calcium homeostasis. Sporadic HPT is caused by the presence of a single parathyroid adenoma in the majority of patients (80–85%) or hyperplasia that affects more than one gland in 15–20% of patients. Sporadic parathyroid carcinoma is an exceedingly rare tumor, responsible for <1% of cases of primary HPT. Parathyroid abnormalities can also present as components of the familial syndrome Hyperparathyroidism Jaw Tumor syndrome (HPT-JT). Abnormalities that are part of the HPT-JT phenotype include parathyroid carcinoma (10–15%), fibro-osseous tumors of...
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. 2002;32:676–80.
Cole AJ, Clifton-Bligh R, Marsh DJ. Histone H2B monoubiquitination: roles to play in human malignancy. Endocr Relat Cancer. 2015;22:T19–33.
Gill AJ, Clarkson A, Gimm O, Keil J, Dralle H, Howell VM, Marsh DJ. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol. 2006;30:1140–9.
Hahn MA, Marsh DJ. Identification of a functional bipartite nuclear localization signal in the tumor suppressor parafibromin. Oncogene. 2005;24:6241–8.
Hahn MA, Marsh DJ. Nucleolar localization of parafibromin is mediated by three nucleolar localization signals. FEBS Lett. 2007;581:5070–4.
Hahn MA, Howell VM, Gill AJ, Clarkson A, Weaire-Buchanan G, Robinson BG, Delbridge L, Gimm O, Schmitt WD, Teh BT, et al. CDC73/HRPT2 CpG island hypermethylation and mutation of 5′-untranslated sequence are uncommon mechanisms of silencing parafibromin in parathyroid tumors. Endocr Relat Cancer. 2010;17:273–82.
Hahn MA, Dickson KA, Jackson S, Clarkson A, Gill AJ, Marsh DJ. The tumor suppressor CDC73 interacts with the ring finger proteins RNF20 and RNF40 and is required for the maintenance of histone 2B monoubiquitination. Hum Mol Genet. 2012;21:559–68.
Howell VM, Haven CJ, Kahnoski K, Khoo SK, Petillo D, Chen J, Fleuren GJ, Robinson BG, Delbridge LW, Philips J, et al. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumors. J Med Genet. 2003;40:657–63.
Jaehning JA. The Paf1 complex: platform or player in RNA polymerase II transcription? Biochim Biophys Acta. 2010;1799:379–88.
Jaenicke LA, von Eyss B, Carstensen A, Wolf E, Xu W, Greifenberg AK, Geyer M, Eilers M, Popov N. Ubiquitin-dependent turnover of MYC antagonizes MYC/PAF1C complex accumulation to drive transcriptional elongation. Mol Cell. 2016;61:54–67.
Lin L, Czapiga M, Nini L, Zhang JH, Simonds WF. Nuclear localization of the parafibromin tumor suppressor protein implicated in the hyperparathyroidism-jaw tumor syndrome enhances its proapoptotic function. Mol Cancer Res. 2007;5:183–93.
Lin L, Zhang JH, Panicker LM, Simonds WF. The parafibromin tumor suppressor protein inhibits cell proliferation by repression of the c-myc proto-oncogene. Proc Natl Acad Sci. 2008;105:17420–5.
Marsh DJ, Hahn MA, Howell VM, Gill AJ. Molecular diagnosis of primary hyperparathyroidism in familial cancer syndromes. Exp Opin Med Diagn. 2007;1:377–92.
Marx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein LS, Cochran C, Skarulis MC, Spiegel AM, Libutti SK, Alexander Jr HR, et al. Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res. 2002;17(Suppl 2):N37–43.
Mosimann C, Hausmann G, Basler K. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo. Cell. 2006;125:327–41.
Shattuck TM, Valimaki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349:1722–9.
Sood R, Bonner TI, Makalowska I, Stephan DA, Robbins CM, Connors TD, Morgenbesser SD, Su K, Faruque MU, Pinkett H, et al. Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus. Genomics. 2001;73:211–22.
Woodard GE, Lin L, Zhang JH, Agarwal SK, Marx SJ, Simonds WF. Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene. 2005;24:1272–6.
Zhang C, Kong D, Tan MH, Pappas Jr DL, Wang PF, Chen J, Farber L, Zhang N, Koo HM, Weinreich M, et al. 2006 Parafibromin inhibits cancer cell growth and causes G1 phase arrest. Biochem Biophys Res Commun. 2006;350:17–24.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Marsh, D.J. (2018). CDC73. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101660
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101660
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences