Cell division cycle protein 73 homolog (CDC73)

CDC73 (Cell division cycle protein 73 homolog), also known as parafibromin, is a nuclear protein encoded by the CDC73 gene and functions predominantly as a tumor suppressor by regulating gene transcription in association with the PAF1 complex and RNA polymerase II[1][2][3][4][5][6]. It modulates the expression of key cell cycle and oncogenic genes (such as c-Myc and cyclin D1) via epigenetic mechanisms (histone methylation and ubiquitination), and interacts with proteins essential for mRNA processing and cytoskeletal dynamics[1][2][4][5]. Germline or somatic mutations lead to tumor predisposition syndromes including hyperparathyroidism-jaw tumor syndrome (HPT-JT), familial isolated hyperparathyroidism, and various forms of carcinoma, making CDC73 a significant diagnostic biomarker and genetic risk factor for neoplasia[3][4][6]. Loss or mutation of parafibromin has profound clinical implications in calcium metabolism and bone diseases, and immunohistochemical parafibromin tests are widely used for tumor diagnosis[1][4][6]. No direct pharmacological therapies exist targeting CDC73 protein function.

Other names

ParafibrominHRPT2C1orf28Hyperparathyroidism 2 proteinFIHPHPTJTHRPT1HYXFamilial isolated hyperparathyroidism proteinPaf1/RNA polymerase II complex component

Mechanisms relevant to targeting parafibromin/CDC73 include restoration of tumor suppressor function or modulation of its regulatory interactions with oncogenic signaling pathways, such as Wnt/β-catenin[1][4]. However, no approved drug acts via these mechanisms on CDC73 directly.