NDRG1 links p53 with proliferation-mediated centrosome homeostasis and genome stability

Proceedings of the National Academy of Sciences of the United States of America
Sarah CroessmannBen Ho Park

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 γ-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.

References

Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Sep 28, 2000·Biochemical and Biophysical Research Communications·H ParkC H Graham
Dec 1, 2000·Nature·B VogelsteinA J Levine
Apr 30, 2003·Cell Death and Differentiation·M Oren
Jul 13, 2004·The Journal of Biological Chemistry·Kyung-Tae KimSam W Lee
Sep 21, 2004·The Journal of Biological Chemistry·Susanne SteinPeng Liang
Dec 3, 2005·Cancer Research·Steven J IsakoffJoan S Brugge
Mar 24, 2007·Nature Reviews. Molecular Cell Biology·Karen H Vousden, David P Lane
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·John P GustinBen Ho Park
Feb 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Surojit SurNickolas Papadopoulos
Jun 10, 2009·Nature·Neil J GanemDavid Pellman
Oct 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Hiroyuki KonishiBen Ho Park
May 9, 2012·EMBO Reports·Andrew J Holland, Don W Cleveland
Jun 21, 2012·Genes & Development·William A Freed-Pastor, Carol Prives
Dec 25, 2012·Nature Cell Biology·Patricia A J Muller, Karen H Vousden
Feb 5, 2013·Cell·Yun-Chi Tang, Angelika Amon
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Mar 22, 2014·Cancer Cell·Patricia A J Muller, Karen H Vousden
Jan 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jonathan R HartPeter K Vogt

❮ Previous
Next ❯

Citations

Apr 1, 2016·Molecular Reproduction and Development·Ruiqin HanLinfang Wang
May 19, 2017·Endocrine-related Cancer·Angela OgdenRitu Aneja
May 26, 2017·Oncotarget·Shuye TianChristopher G Proud
Feb 13, 2017·Breast Cancer Research and Treatment·Sarah CroessmannBen Ho Park
Jun 15, 2018·Breast Cancer Research : BCR·Christopher J SevinskyDouglas S Conklin
Dec 19, 2020·Neuromuscular Disorders : NMD·Fredrik S SkedsmoKarin H Jäderlund

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.