{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:38:20Z","timestamp":1789601900399,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    In this review, we discuss parafibromin protein, which is encoded by\n                    <jats:italic>CDC73<\/jats:italic>\n                    . A mutation in this gene causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disease.\n                    <jats:italic>CDC73<\/jats:italic>\n                    is transcriptionally downregulated by the Wilms\u2019 tumor suppressor gene WT1 and translationally targeted by miR-182-3p and miR-155. In the nucleus, parafibromin binds to RNA polymerase II and PAF1 complex for transcription. Parafibromin transcriptionally increases the expression of c-Myc, decreases CPEB1 expression by interacting with H3M4, and reduces cyclin D1 expression by binding to H3K9. The RNF20\/RNF40\/parafibromin complex induces monoubiquitination of H2B-K120, and SHP2-mediated dephosphorylation of parafibromin promotes the parafibromin\/\u03b2-catenin interaction and induces the expression of Wnt target genes, which is blocked by PTK6-medidated phosphorylation. Parafibromin physically associates with the CPSF and CstF complexes that are essential for\n                    <jats:italic>INTS6<\/jats:italic>\n                    mRNA maturation. In the cytosol, parafibromin binds to hSki8 and eEF1B\u03b3 for the destabilization of p53 mRNA, to JAK1\/2-STAT1 for STAT1 phosphorylation, and to actinin-2\/3 to bundle\/cross-link actin filaments. Mice with\n                    <jats:italic>CDC73<\/jats:italic>\n                    knockout in the parathyroid develop parathyroid and uterine tumors and are used as a model for HPT-JT syndrome. Conditional deletion of\n                    <jats:italic>CDC73<\/jats:italic>\n                    in mesenchymal progenitors results in embryos with agenesis of the heart and liver while its abrogation in mature osteoblasts and osteocytes increases cortical and trabecular bone. Heterozygous germline mutations in\n                    <jats:italic>CDC73<\/jats:italic>\n                    are associated with parathyroid carcinogenesis. The rates of\n                    <jats:italic>CDC73<\/jats:italic>\n                    mutation and parafibromin loss decrease from parathyroid adenoma to atypical adenoma to carcinoma. In addition, down-regulated parafibromin is closely linked to the tumorigenesis, subsequent progression, or poor prognosis of head and neck, gastric, lung, colorectal, and ovarian cancers, and its overexpression might reverse the aggressiveness of these cancer cells. Therefore, parafibromin might be useful as a biological marker of malignancies and a target for their gene therapy.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2022.1006400","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T01:50:57Z","timestamp":1663725057000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The roles of the tumor suppressor parafibromin in cancer"],"prefix":"10.3389","volume":"10","author":[{"given":"Hua-chuan","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong-yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1476-4598-7-65","article-title":"The parafibromin tumor suppressor protein interacts with actin-binding proteins actinin-2 and actinin-3","volume":"7","author":"Agarwal","year":"2008","journal-title":"Mol. 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