Novel function of orphan nuclear receptor Nur77 in stabilizing hypoxia-inducible factor-1alpha

The Journal of Biological Chemistry
Young-Gun YooMi-Ock Lee

Abstract

Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis by inducing the expression of a broad range of genes in a hypoxia-dependent manner. Here, we show that the orphan nuclear receptor Nur77 is an important regulator of HIF-1alpha. Under hypoxic conditions, Nur77 protein and transcripts were induced in a time-dependent manner. When Nur77 was exogenously introduced, it enhanced the transcriptional activity of HIF-1, whereas the dominant negative Nur77 mutant abolished the function of HIF-1. The HIF-1alpha protein was greatly increased and completely localized in the nucleus when coexpressed with Nur77. The N-terminal transactivation domain of Nur77 was required and sufficient for the activation of HIF-1alpha. The association of HIF-1alpha with von Hippel-Lindau protein was not affected, whereas that with mouse double minute 2 (MDM2) was greatly reduced in the presence of Nur77. Further we found that the expression of MDM2 was repressed at transcription level in the presence of Nur77 as well as under hypoxic conditions. Finally, PD98059 decreased Nur77-induced HIF-1alpha stability and recovered MDM2 expression, indicating that the extracellular signal-regulated kinase pathway is critical in the N...Continue Reading

References

Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·T G HazelL F Lau
Nov 1, 1995·Molecular and Cellular Biology·J D WoroniczA Winoto
Oct 7, 1997·Molecular and Cellular Biology·A PhilipsJ Drouin
May 5, 1998·Molecular and Cellular Biology·C SchmaltzD E Fisher
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·L E HuangH F Bunn
Feb 26, 1999·The Journal of Biological Chemistry·P J KallioL Poellinger
Jun 6, 2000·The Journal of Biological Chemistry·D E RichardJ Pouyssegur
Jul 6, 2000·Nature Cell Biology·Y KatagiriG Guroff
Sep 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·T KamuraJ W Conaway
Feb 22, 2001·Journal of the National Cancer Institute·M Höckel, P Vaupel
Aug 23, 2001·Trends in Molecular Medicine·G L Semenza
Nov 9, 2001·Biochemical and Biophysical Research Communications·M O LeeS J Kim
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Feb 28, 2002·Molecular and Cellular Biology·Ester M HammondAmato J Giaccia
Mar 9, 2002·Biochemical and Biophysical Research Communications·Hege H SlagsvoldRagnhild E Paulsen
Apr 12, 2002·The Journal of Biological Chemistry·Yonghua ZhuDavid A Greenberg
Apr 19, 2002·Carcinogenesis·Dania Alarcon-Vargas, Ze'ev Ronai
May 2, 2002·Cell·Astar Winoto, Dan R Littman
Aug 21, 2002·The Journal of Biological Chemistry·Denise A ChanAmato J Giaccia
Nov 12, 2002·The EMBO Journal·Akihiro ItoTso-Pang Yao
Apr 3, 2003·Biochemical and Biophysical Research Communications·Catherine L CioffiBenjamin R Bowen
Jun 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shinobu SuzukiWen-Chen Yeh
Nov 13, 2003·Molecular and Cellular Biology·Siva Kumar KolluriXiao-kun Zhang

❮ Previous
Next ❯

Citations

Mar 28, 2007·Pathology Oncology Research : POR·Andrzej WincewiczStanislaw Sulkowski
Apr 12, 2007·Cell Research·Hang-Zi Chen, Qiao Wu
Dec 13, 2012·Science Signaling·Savithri BalasubramanianTerry B Strom
Oct 20, 2005·Science's STKE : Signal Transduction Knowledge Environment·Roland H WengerGieri Camenisch
Sep 2, 2009·Molecular and Cellular Biology·Lluis MartorellJosé Martínez-González
Feb 29, 2008·Experimental & Molecular Medicine·Bu Yeon KimHong Duk Youn
Nov 13, 2013·Annual Review of Physiology·Sung Hee Baek, Keun Il Kim
Dec 8, 2006·Expert Opinion on Therapeutic Targets·Xiao-kun Zhang
Apr 28, 2012·Expert Opinion on Therapeutic Targets·Sally K Y ToAlice S T Wong
Jun 21, 2011·Cancer radiothérapie : journal de la Société française de radiothérapie oncologique·C ChargariE Deutsch
Jul 1, 2014·Biochimica Et Biophysica Acta·Kondababu KurakulaCarlie J M de Vries
Dec 21, 2017·Oncogene·Ninel AzoiteiThomas Seufferlein
Jul 29, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Eun-Jin KimMi-Ock Lee
Dec 2, 2006·The EMBO Journal·Bi-xing ZhaoQiao Wu
Jan 18, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·James P LuyendykRobert A Roth
Jun 5, 2014·International Journal of Cancer. Journal International Du Cancer·James L Thorne, Moray J Campbell
Apr 1, 2015·Molecular & Cellular Oncology·Ninel AzoiteiThomas Seufferlein
Jan 22, 2020·The Journal of Clinical Investigation·Ryan J AshleyLionel Blanc
Nov 28, 2020·Bioscience Reports·Xiuru ZhangGulimiran Alitongbieke
Jan 18, 2008·Cancer Research·Veronica A Carroll, Margaret Ashcroft
Feb 19, 2021·Frontiers in Endocrinology·Livia OdagiuNathalie Labrecque

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.