{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CDC73, also known as HRPT2, encodes the highly conserved 531–amino‐acid protein parafibromin, which functions as a critical tumor suppressor. Initial studies identified inactivating germline and somatic CDC73/HRPT2 mutations predominantly in hyperparathyroidism‐jaw tumor syndrome and in parathyroid carcinomas, establishing its central role in parathyroid tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functional analyses have revealed that parafibromin is predominantly a nuclear protein that associates with key transcription regulatory players. In particular, parafibromin is an integral component of the Polymerase-Associated Factor 1 (PAF1) complex, interacting directly with other complex members as well as RNA polymerase II to regulate transcription initiation, elongation, and coupled mRNA 3’ end processing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Through these interactions, parafibromin participates in histone modification events—such as enhancing H3K4 methylation—and coordinates the recruitment of RNA-processing factors. These mechanisms underlie its ability to control the expression of critical cell cycle regulators including cyclin D1 and c-myc, and thus to inhibit cell proliferation; disruption of such regulatory pathways contributes to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, emerging evidence suggests that CDC73/parafibromin functions extend to regulating mRNA maturation by facilitating the association of 3′ end processing factors with actively transcribed chromatin, further linking aberrant mRNA processing to tumor development. Down-regulation of CDC73 has also been documented in other malignancies, with studies implicating microRNAs in its deregulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CDC73 encodes parafibromin, a multifunctional protein that safeguards normal cell growth by integrating transcriptional regulation, chromatin modifications, and mRNA processing. Loss or inactivation of CDC73 disrupts these processes and leads to deregulated expression of oncogenic factors, thereby contributing to tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J D Carpten, C M Robbins, A Villablanca, et al. 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