title: Parafibromin inhibits cancer cell growth and causes G1 phase arrest.
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.
authors.affiliation: Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Kong
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.forename: Donald L
authors.initials: DL
authors.lastname: Pappas
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.forename: Jindong
authors.initials: J
authors.lastname: Chen
authors.forename: Leslie
authors.initials: L
authors.lastname: Farber
authors.forename: Nian
authors.initials: N
authors.lastname: Zhang
authors.forename: Han-Mo
authors.initials: HM
authors.lastname: Koo
authors.forename: Michael
authors.initials: M
authors.lastname: Weinreich
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins