Croessmann_2015_Proc.Natl.Acad.Sci.U.S.A_112_11583

Reference

Title : NDRG1 links p53 with proliferation-mediated centrosome homeostasis and genome stability - Croessmann_2015_Proc.Natl.Acad.Sci.U.S.A_112_11583
Author(s) : Croessmann S , Wong HY , Zabransky DJ , Chu D , Mendonca J , Sharma A , Mohseni M , Rosen DM , Scharpf RB , Cidado J , Cochran RL , Parsons HA , Dalton WB , Erlanger B , Button B , Cravero K , Kyker-Snowman K , Beaver JA , Kachhap S , Hurley PJ , Lauring J , Park BH
Ref : Proc Natl Acad Sci U S A , 112 :11583 , 2015
Abstract :

The tumor protein 53 (TP53) tumor suppressor gene is the most frequently somatically altered gene in human cancers. Here we show expression of N-Myc down-regulated gene 1 (NDRG1) is induced by p53 during physiologic low proliferative states, and mediates centrosome homeostasis, thus maintaining genome stability. When placed in physiologic low-proliferating conditions, human TP53 null cells fail to increase expression of NDRG1 compared with isogenic wild-type controls and TP53 R248W knockin cells. Overexpression and RNA interference studies demonstrate that NDRG1 regulates centrosome number and amplification. Mechanistically, NDRG1 physically associates with gamma-tubulin, a key component of the centrosome, with reduced association in p53 null cells. Strikingly, TP53 homozygous loss was mutually exclusive of NDRG1 overexpression in over 96% of human cancers, supporting the broad applicability of these results. Our study elucidates a mechanism of how TP53 loss leads to abnormal centrosome numbers and genomic instability mediated by NDRG1.

PubMedSearch : Croessmann_2015_Proc.Natl.Acad.Sci.U.S.A_112_11583
PubMedID: 26324937

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Citations formats

Croessmann S, Wong HY, Zabransky DJ, Chu D, Mendonca J, Sharma A, Mohseni M, Rosen DM, Scharpf RB, Cidado J, Cochran RL, Parsons HA, Dalton WB, Erlanger B, Button B, Cravero K, Kyker-Snowman K, Beaver JA, Kachhap S, Hurley PJ, Lauring J, Park BH (2015)
NDRG1 links p53 with proliferation-mediated centrosome homeostasis and genome stability
Proc Natl Acad Sci U S A 112 :11583

Croessmann S, Wong HY, Zabransky DJ, Chu D, Mendonca J, Sharma A, Mohseni M, Rosen DM, Scharpf RB, Cidado J, Cochran RL, Parsons HA, Dalton WB, Erlanger B, Button B, Cravero K, Kyker-Snowman K, Beaver JA, Kachhap S, Hurley PJ, Lauring J, Park BH (2015)
Proc Natl Acad Sci U S A 112 :11583