Parafibromin inhibits cancer cell growth and causes G1 phase arrest

• DOI: 10.1016/j.bbrc.2006.08.169
• Publication Date: 2006-09-08T19:17:14Z
• Authors: Chun Zhang; Dong Kong; Min-Han Tan; Donald L. Pappas; Peng-Fei Wang; Jindong Chen; Leslie Farber; Nian Zhang; Han-Mo Koo; Michael Weinreich; Bart O. Williams; Bin Tean Teh
• Keywords: Cell Nucleus; 0301 basic medicine; Tumor Suppressor Proteins; G1 Phase; Cell Line; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Neoplasms; Chlorocebus aethiops; Mutation; Animals; Humans; Cell Proliferation

The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative properties. We show that overexpression of parafibromin inhibits colony formation and cellular proliferation, and induces cell cycle arrest in the G1 phase. Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant-negative manner by abolishing the ability of parafibromin to suppress cell proliferation. These findings suggest that parafibromin has a critical role in cell growth, and mutations in HRPT2 can directly inhibit this role.