Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms

EMBO Reports
Robert StadAart G Jochemsen

Abstract

The p53 protein maintains genomic integrity through its ability to induce cell cycle arrest or apoptosis in response to various forms of stress. Substantial regulation of p53 activity occurs at the level of protein stability, largely determined by the activity of the Mdm2 protein. Mdm2 targets both p53 and itself for ubiquitylation and subsequent proteasomal degradation by acting as an ubiquitin ligase, a function that needs an intact Mdm2 RING finger. For efficient degradation of p53 nuclear export appears to be required. The Mdmx protein, structurally homologous to Mdm2, does not target p53 for degradation, but even stabilizes both p53 and Mdm2, an activity most likely mediated by heterodimerization of the RING fingers of Mdm2 and Mdmx. Here we show that Mdmx expression leads to accumulation of ubiquitylated, nuclear p53 but does not significantly affect the Mdm2-mediated ubiquitylation of p53. In contrast, Mdmx stabilizes Mdm2 by inhibiting its self-ubiquitylation.

References

May 15, 1997·Nature·Y HauptM Oren
May 15, 1997·Nature·M H KubbutatK H Vousden
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·W Tao, A J Levine
Dec 23, 1999·The Journal of Biological Chemistry·D A SharpD L George
Jan 11, 2000·Molecular and Cellular Biology·M W Jackson, S J Berberich
Mar 18, 2000·The Journal of Biological Chemistry·S FangA M Weissman
May 29, 2000·The Journal of Biological Chemistry·R StadA G Jochemsen
Sep 12, 2000·Nature Cell Biology·S D BoydT Jacks
Sep 12, 2000·Nature Cell Biology·R K GeyerC G Maki

❮ Previous
Next ❯

Citations

Mar 25, 2010·Molecular Biology Reports·Lan WangLong Yu
Jun 1, 2005·Biochimica Et Biophysica Acta·Leena Latonen, Marikki Laiho
May 24, 2005·Biochemical and Biophysical Research Communications·Yu Pan, Jiandong Chen
Jan 16, 2002·Current Opinion in Genetics & Development·Dan Michael, Moshe Oren
Jan 1, 2003·Seminars in Cancer Biology·Dan Michael, Moshe Oren
Apr 1, 2004·Molecular Cell·Muyang LiWei Gu
Oct 1, 2013·Expert Reviews in Molecular Medicine·R KosterS de Jong
Jan 12, 2010·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Mei LiangCarlos E Bueso-Ramos
Dec 5, 2006·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Xin HanCarlos E Bueso-Ramos
Nov 26, 2009·Nature Reviews. Cancer·Christopher J BrownDavid P Lane
Aug 24, 2011·Nature Reviews. Molecular Cell Biology·Allan M WeissmanAaron Ciechanover
Feb 9, 2010·Oncogene·S LamA G Jochemsen
Feb 27, 2007·Oncogene·H F Horn, K H Vousden
Jul 21, 2009·The Journal of Biological Chemistry·Peter TsvetkovYosef Shaul
Jan 19, 2010·The Journal of Biological Chemistry·Damon ReedMichael A Dyer
Aug 14, 2010·The Journal of Biological Chemistry·Saravanakumar IyappanMartin Scheffner
Nov 19, 2010·The Journal of Biological Chemistry·Jonathan ShloushCheryl H Arrowsmith
Nov 18, 2010·The Journal of Biological Chemistry·David L WaningLindsey D Mayo
Aug 7, 2002·DNA and Cell Biology·Peter Sabbatini, Frank McCormick
Sep 22, 2010·Molecular and Cellular Biology·Sarah De ClercqJean-Christophe Marine
Sep 1, 2006·Molecular and Cellular Biology·Yaron PeregAart G Jochemsen
Jan 4, 2008·Molecular and Cellular Biology·Daniele M GilkesJiandong Chen
Jul 9, 2002·Molecular and Cellular Biology·Domenico MiglioriniJean-Christophe Marine
Oct 9, 2002·Molecular and Cellular Biology·Changgong LiJiandong Chen
Jul 2, 2003·Molecular and Cellular Biology·Erik MeulmeesterAart G Jochemsen
Jul 2, 2003·Molecular and Cellular Biology·Hidehiko KawaiZhi-Min Yuan
Jul 16, 2003·Molecular and Cellular Biology·Yu Pan, Jiandong Chen
Jun 17, 2004·Molecular and Cellular Biology·Davide DanoviJean-Christophe Marine
Nov 16, 2004·Molecular and Cellular Biology·Francisco M VegaPedro A Lazo
Jul 19, 2005·Molecular and Cellular Biology·Lihong ChenJiandong Chen
Feb 16, 2006·Molecular and Cellular Biology·Yi DingDuen-Hwa Yan
Jun 24, 2008·Molecular Cancer Research : MCR·Juan A BarbozaGuillermina Lozano
Nov 15, 2012·Genes & Cancer·Maurisa F Riley, Guillermina Lozano
Feb 23, 2010·PLoS Computational Biology·Sohyoung KimKurt W Kohn
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Shunbin XiongGuillermina Lozano
Jul 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yunyuan V WangGeoffrey M Wahl
Mar 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yaron PeregYosef Shiloh
Sep 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Laëtitia K LinaresMartin Scheffner
May 17, 2014·Chemical Reviews·Vladimir N UverskyAndreas C Joerger

❮ 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.