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Parafibromin inhibits cancer cell growth and causes G1 phase arrest

by 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 show all authors
Biochemical and Biophysical Research Communications ()

Abstract

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. ?? 2006 Elsevier Inc. All rights reserved.

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