Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner

Proceedings of the National Academy of Sciences of the United States of America
Hee Jung YangXinbin Chen

Abstract

WT p53 is critical for tumor suppression, whereas mutant p53 promotes tumor progression. Nerve injury-induced protein 1 (Ninj1) is a target of p53 and forms a feedback loop with p53 by repressing p53 mRNA translation. Here, we show that loss of Ninj1 increased mutant p53 expression and, subsequently, enhanced cell growth and migration in cells carrying a mutant p53. In contrast, loss of Ninj1 inhibited cell growth and migration in cells carrying a WT p53. To explore the biological significance of Ninj1, we generated a cohort of Ninj1-deficient mice and found that Ninj1 +/- mice were prone to systemic inflammation and insulitis, but not to spontaneous tumors. We also found that loss of Ninj1 altered the tumor susceptibility in both mutant p53 and p53-null background. Specifically, in a mutant p53(R270H) background, Ninj1 deficiency shortened the lifespan, altered the tumor spectrum, and increased tumor burden, likely via enhanced expression of mutant p53. In a p53-null background, Ninj1 deficiency significantly increased the incidence of T-lymphoblastic lymphoma. Taken together, our data suggest that depending on p53 genetic status, Ninj1 has two opposing functions in tumorigenesis and that the Ninj1-p53 loop may be targeted to...Continue Reading

References

May 1, 1996·Genes & Development·L J Ko, C Prives
Aug 22, 1997·The Journal of Biological Chemistry·T ArakiJ Milbrandt
Dec 1, 2000·Nature·B VogelsteinA J Levine
May 2, 2001·Nature Cell Biology·A JacintoP Martin
May 15, 2002·Human Mutation·Magali OlivierPierre Hainaut
Nov 5, 2002·Nature Medicine·Simona FrigerioLuca Piali
Apr 20, 2004·Cellular and Molecular Life Sciences : CMLS·K HarmsX Chen
Nov 19, 2004·Cancer Research·Lilach WeiszVarda Rotter
May 17, 2008·Genes & Development·Tamara TerzianGuillermina Lozano
May 5, 2009·Cell·Karen H Vousden, Carol Prives
Aug 21, 2009·Nature Reviews. Cancer·Ran Brosh, Varda Rotter
Nov 17, 2009·Cancer Investigation·Nektaria MakriliaKostas Syrigos
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Moshe Oren, Varda Rotter
Feb 25, 2011·Nature Reviews. Molecular Cell Biology·Ugo Cavallaro, Elisabetta Dejana
Mar 8, 2011·Cytokine & Growth Factor Reviews·Markus F Neurath, Susetta Finotto
Jul 19, 2011·Genes & Development·Jin ZhangXinbin Chen
Jun 21, 2012·Genes & Development·William A Freed-Pastor, Carol Prives
Aug 24, 2012·Nature·Francesca OdoardiAlexander Flügel
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Seong-Jun ChoXinbin Chen
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Dec 19, 2013·The Journal of Biological Chemistry·Bum Ju AhnKyu-Won Kim
Mar 22, 2014·Cancer Cell·Patricia A J Muller, Karen H Vousden
Jul 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Guo Nan YinJun-Kyu Suh
Dec 17, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhangXinbin Chen
Mar 15, 2015·Circulation Journal : Official Journal of the Japanese Circulation Society·Motoki MatsukiJun-ichi Kawabe
Apr 11, 2015·American Journal of Respiratory Cell and Molecular Biology·Carla JenneweinKai Zacharowski
Jan 28, 2016·International Journal of Cancer. Journal International Du Cancer·Yeong-Su JangSeung Hyun Oh

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Citations

Apr 19, 2020·The Journal of Pathology·Jin ZhangXinbin Chen
Jul 25, 2019·Oncogene·Yanhong ZhangXinbin Chen
Feb 1, 2019·Experimental & Molecular Medicine·Sung-Jin BaeKyu-Won Kim
Nov 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhangXinbin Chen
Jan 23, 2020·International Journal of Molecular Sciences·Hyun Jin JungSeung Hyun Oh
May 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hoon ChoiKyu-Won Kim
Jan 18, 2020·Anatomy & Cell Biology·Poornima EkanayakeTaekyun Shin
Dec 29, 2018·Cancer Research·Christopher A LucchesiXinbin Chen
Jan 21, 2021·Nature·Nobuhiko KayagakiVishva M Dixit
Mar 24, 2021·Journal of Cellular Physiology·Bin HeJianyan Wen
Sep 20, 2021·Journal of Molecular Biology·Skylar S WrightVijay A Rathinam

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