Parafibromin inhibits cancer cell growth and causes G1 phase arrest.
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.
Zhang
Chun
C
Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Kong
Dong
D
Tan
Min-Han
MH
Pappas
Donald L
DL
Wang
Peng-Fei
PF
Chen
Jindong
J
Farber
Leslie
L
Zhang
Nian
N
Koo
Han-Mo
HM
Weinreich
Michael
M
Williams
Bart O
BO
Teh
Bin Tean
BT
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*
C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins