MDM2

Summary

Gene Symbol: MDM2
Description: MDM2 proto-oncogene
Alias: ACTFS, HDMX, hdm2, E3 ubiquitin-protein ligase Mdm2, MDM2 oncogene, E3 ubiquitin protein ligase, MDM2 proto-oncogene, E3 ubiquitin protein ligase, Mdm2, p53 E3 ubiquitin protein ligase homolog, Mdm2, transformed 3T3 cell double minute 2, p53 binding protein, double minute 2, human homolog of; p53-binding protein, oncoprotein Mdm2
Species: human

Top Publications

  1. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
  2. pmc MDM2, MDMX and p53 in oncogenesis and cancer therapy
    Mark Wade
    Center for Genomic Science of Fondazione Istituto Italiano di Tecnologia, Via Adamello 16, 20139 Milan, Italy
    Nat Rev Cancer 13:83-96. 2013
  3. ncbi Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
    R Honda
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan
    FEBS Lett 420:25-7. 1997
  4. ncbi ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways
    Y Zhang
    Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, 27599 3280, USA
    Cell 92:725-34. 1998
  5. ncbi Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5
    Mu Shui Dai
    Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 279:44475-82. 2004
  6. ncbi Amplification of a gene encoding a p53-associated protein in human sarcomas
    J D Oliner
    Department of Pediatrics, University of Michigan Cancer Center, Ann Arbor 48109
    Nature 358:80-3. 1992
  7. ncbi A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans
    Gareth L Bond
    Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA
    Cell 119:591-602. 2004
  8. pmc Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha
    R Ravi
    Johns Hopkins Oncology Center, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 USA
    Genes Dev 14:34-44. 2000
  9. ncbi The p53-Mdm2 module and the ubiquitin system
    Dan Michael
    Department of Molecular Cell Biology, Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel
    Semin Cancer Biol 13:49-58. 2003
  10. ncbi Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 function
    D Chen
    Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Oncogene 26:5029-37. 2007

Research Grants

  1. Regulation of Mdm2 compartmentalization
    Lindsey Mayo; Fiscal Year: 2009
  2. Mechanisms of Mdm2/Mdmx in repressing p53
    Wei Gu; Fiscal Year: 2013
  3. KAREN ELIZABETH POLLOK; Fiscal Year: 2014
  4. Amato J Giaccia; Fiscal Year: 2014
  5. Zhenkun Lou; Fiscal Year: 2015
  6. Molecular Mechanism of Mule in DNA Damage Response and Tumorigenesis
    Qing Zhong; Fiscal Year: 2013
  7. Michael B Kastan; Fiscal Year: 2016
  8. PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
    Nelson Fausto; Fiscal Year: 2010
  9. Regulation of the ATM/ATR-p53 DNA Damage Signaling Pathway by the Wip1 Phosphatas
    Xiongbin Lu; Fiscal Year: 2013
  10. Role of p53 in cell cycle checkpoints
    James J Manfredi; Fiscal Year: 2013

Detail Information

Publications352 found, 100 shown here

  1. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
    b>MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function...
  2. pmc MDM2, MDMX and p53 in oncogenesis and cancer therapy
    Mark Wade
    Center for Genomic Science of Fondazione Istituto Italiano di Tecnologia, Via Adamello 16, 20139 Milan, Italy
    Nat Rev Cancer 13:83-96. 2013
    The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor...
  3. ncbi Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
    R Honda
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan
    FEBS Lett 420:25-7. 1997
    ..p53 was polyubiquitinated in the presence of E1, UbcH5 as E2 and MDM2 oncoprotein...
  4. ncbi ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways
    Y Zhang
    Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, 27599 3280, USA
    Cell 92:725-34. 1998
    ..We show here that ARF binds to MDM2 and promotes the rapid degradation of MDM2...
  5. ncbi Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5
    Mu Shui Dai
    Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 279:44475-82. 2004
    The oncoprotein MDM2 associates with ribosomal proteins L5, L11, and L23. Both L11 and L23 have been shown to activate p53 by inhibiting MDM2-mediated p53 suppression. Here we have shown that L5 also activates p53...
  6. ncbi Amplification of a gene encoding a p53-associated protein in human sarcomas
    J D Oliner
    Department of Pediatrics, University of Michigan Cancer Center, Ann Arbor 48109
    Nature 358:80-3. 1992
    ..b>MDM2 is a strong candidate for one such cellular protein; the MDM2 gene was originally identified by virtue of its ..
  7. ncbi A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans
    Gareth L Bond
    Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA
    Cell 119:591-602. 2004
    ..A central node in the p53 pathway is the MDM2 protein, a direct negative regulator of p53...
  8. pmc Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha
    R Ravi
    Johns Hopkins Oncology Center, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 USA
    Genes Dev 14:34-44. 2000
    ..We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1),..
  9. ncbi The p53-Mdm2 module and the ubiquitin system
    Dan Michael
    Department of Molecular Cell Biology, Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel
    Semin Cancer Biol 13:49-58. 2003
    ..The ubiquitination and degradation of p53 are largely controlled by Mdm2, an oncogenic E3 ligase...
  10. ncbi Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 function
    D Chen
    Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Oncogene 26:5029-37. 2007
    As a major negative regulator of p53, the MDM2 oncogene plays an important role in carcinogenesis and tumor progression. MDM2 promotes p53 proteasomal degradation and negatively regulates p53 function...
  11. pmc Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53
    Saurabh Dayal
    CR UK Cell Transformation Research Group, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland
    J Biol Chem 284:5030-41. 2009
    Both p53 and its repressor Mdm2 are subject to ubiquitination and proteasomal degradation. We show that knockdown of the deubiquitinating enzyme USP5 (isopeptidase T) results in an increase in the level and transcriptional activity of p53...
  12. ncbi MDM2 interacts with MDMX through their RING finger domains
    S Tanimura
    Institute of Life Sciences, Kurume University, Japan
    FEBS Lett 447:5-9. 1999
    The N-terminus of MDM2 proto-oncoprotein interacts with p53 and down modulates p53 activity by inhibiting transcriptional activity and promoting p53 degradation. MDMX is structurally related to MDM2 and also binds to p53...
  13. pmc ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
    R Maya
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Genes Dev 15:1067-77. 2001
    ..p53 is phosphorylated by ATM shortly after DNA damage, resulting in enhanced stability and activity of p53. The Mdm2 oncoprotein is a pivotal negative regulator of p53...
  14. pmc USP10 regulates p53 localization and stability by deubiquitinating p53
    Jian Yuan
    Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
    Cell 140:384-96. 2010
    ..Ubiquitination by the E3 ubiquitin ligase Mdm2 is the major regulatory mechanism of p53, which induces p53 nuclear export and degradation...
  15. pmc The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex
    Min Sup Song
    National Research Laboratory for Genomic Stability, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
    EMBO J 27:1863-74. 2008
    ..Under normal conditions, the antiproliferative effects of p53 are inhibited by MDM2, a ubiquitin ligase that promotes p53 ubiquitination and degradation. MDM2 is also self-ubiquitinated and degraded...
  16. ncbi Differential binding of p53 and nutlin to MDM2 and MDMX: computational studies
    Thomas Leonard Joseph
    Bioinformatics Institute A STAR, Matrix, Singapore
    Cell Cycle 9:1167-81. 2010
    ..One such defect is the overexpression of the MDM2 and MDMX proteins. This has led to an intense effort to develop inhibitors of p53-MDM2/MDMX interactions...
  17. pmc MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation
    Akihiro Ito
    Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA
    EMBO J 21:6236-45. 2002
    ..p300/CBP-mediated acetylation of p53 is negatively regulated by MDM2. Here we show that MDM2 can promote p53 deacetylation by recruiting a complex containing HDAC1...
  18. ncbi Regulation of HDM2 activity by the ribosomal protein L11
    Marion A E Lohrum
    Regulation of Cell Growth Laboratory, NCI FRCDC, Frederick, MD 21702, USA
    Cancer Cell 3:577-87. 2003
    The HDM2 protein plays an important role in regulating the stability and function of the p53 tumor suppressor protein...
  19. ncbi Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation
    Sari Kurki
    Haartman Institute and Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, P O Box 63, FIN 00014 Helsinki, Helsinki, Finland
    Cancer Cell 5:465-75. 2004
    ..we show that NPM is a UV damage response protein that undergoes nucleoplasmic redistribution and regulates p53 and HDM2 levels and their interaction...
  20. pmc Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
    T Kamijo
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 95:8292-7. 1998
    ..ARF retrovirus, we determined that mouse p19(ARF) can interact directly with p53, as well as with the p53 regulator mdm2. ARF can bind p53-DNA complexes, and it depends upon functional p53 to transcriptionally induce mdm2 and the cyclin-..
  21. pmc ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage
    Lihong Chen
    Molecular Oncology Program, H Lee Moffitt Comprehensive Cancer Center and Research Institute, Tampa, FL 33612, USA
    EMBO J 24:3411-22. 2005
    ..Rapid activation of p53 by ionizing radiation is dependent on signaling by the ATM kinase. MDM2 and MDMX are important p53 regulators and logical targets for stress signals...
  22. doi Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans
    K Linke
    Department of Biochemistry, University of Otago, Dunedin, New Zealand
    Cell Death Differ 15:841-8. 2008
    b>MDM2, a ubiquitin E3-ligase of the RING family, has a key role in regulating p53 abundance. During normal non-stress conditions p53 is targeted for degradation by MDM2. MDM2 can also target itself and MDMX for degradation...
  23. pmc The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2
    F J Stott
    Imperial Cancer Research Fund Laboratories, P O Box 123, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO J 17:5001-14. 1998
    ..the product of the human CDKN2A beta transcript, p14(ARF), activates a p53 response manifest in elevated levels of MDM2 and p21(CIP1) and cell cycle arrest in both G1 and G2/M...
  24. pmc The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2
    Lauren F Stevenson
    CR UK Cell Transformation Research Group, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    EMBO J 26:976-86. 2007
    b>Mdm2 is an E3 ubiquitin ligase that promotes its own ubiquitination and also ubiquitination of the p53 tumour suppressor...
  25. pmc Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26
    Ying Zhang
    State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China
    Nucleic Acids Res 38:6544-54. 2010
    b>HDM2 is a p53-specific E3 ubiquitin ligase. Its overexpression leads to excessive inactivation of tumor protein p53, diminishing its tumor suppressor function...
  26. ncbi Cyclin G recruits PP2A to dephosphorylate Mdm2
    Koji Okamoto
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Mol Cell 9:761-71. 2002
    ..Interestingly, cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216...
  27. pmc Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase
    Hui Kuan Lin
    George H Whipple Laboratory for Cancer Research, Department of Pathology and The Cancer Center, University of Rochester, Rochester, NY 14642, USA
    EMBO J 21:4037-48. 2002
    ..Here we show that Akt and Mdm2 form a complex with AR and promote phosphorylation-dependent AR ubiquitylation, resulting in AR degradation by the ..
  28. ncbi Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity
    Dimitris P Xirodimas
    University of Dundee, Ninewells Hospital and Medical School, Department of Surgery and Molecular Oncology, Dundee DD1 9SY, UK
    Cell 118:83-97. 2004
    ..Here, we show that the Mdm2 RING finger E3 ubiquitin ligase can also promote NEDD8 modification of the p53 tumor suppressor protein...
  29. pmc ATM activates p53 by regulating MDM2 oligomerization and E3 processivity
    Qian Cheng
    Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL, USA
    EMBO J 28:3857-67. 2009
    ..We show in this report that ATM induces p53 accumulation by phosphorylating the ubiquitin E3 ligase MDM2. Multiple ATM target sites near the MDM2 RING domain function in a redundant manner to provide robust DNA damage ..
  30. doi The MDM2 promoter SNP285C/309G haplotype diminishes Sp1 transcription factor binding and reduces risk for breast and ovarian cancer in Caucasians
    Stian Knappskog
    Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
    Cancer Cell 19:273-82. 2011
    b>MDM2 plays a key role in modulating p53 function. The MDM2 SNP309T > G promoter polymorphism enhances Sp1 binding and has been linked to cancer risk and young age at diagnosis although with conflicting evidence...
  31. pmc Novel insights into the molecular mechanisms governing Mdm2 ubiquitination and destruction
    Hiroyuki Inuzuka
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
    Oncotarget 1:685-90. 2010
    The Mdm2/p53 pathway is compromised in more than 50% of all human cancers, therefore it is an intensive area of research to understand the upstream regulatory pathways governing Mdm2/p53 activity...
  32. pmc MdmX protein is essential for Mdm2 protein-mediated p53 polyubiquitination
    Xinjiang Wang
    Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
    J Biol Chem 286:23725-34. 2011
    Genetic evidence has implicated both Mdm2 and MdmX as essential in negative regulation of p53. However, the exact role of MdmX in this Mdm2-dependent protein degradation is not well understood...
  33. doi TRIM8 modulates p53 activity to dictate cell cycle arrest
    Mariano Francesco Caratozzolo
    Institute for Biomedical Technologies, National Research Council, Bari, Italy
    Cell Cycle 11:511-23. 2012
    ..Concurrently, TRIM8 overexpression induced the degradation of the MDM2 protein, the principal regulator of p53 stability...
  34. pmc SUMO-1 modification activates the transcriptional response of p53
    M S Rodriguez
    School of Biomedical Science, BMS Building, University of St Andrews, St Andrews, Fife KY16 9ST
    EMBO J 18:6455-61. 1999
    ..In normal cells p53 is constitutively ubiquitylated by the Mdm2 ubiquitin ligase...
  35. ncbi Transformation of normal human cells in the absence of telomerase activation
    Yvette R Seger
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Cancer Cell 2:401-13. 2002
    ..Here we report that the combined expression of adenovirus E1A, Ha-RasV12, and MDM2 is sufficient to convert a normal human cell into a cancer cell...
  36. ncbi MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein
    Patima Sdek
    Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA
    Mol Cell 20:699-708. 2005
    ..b>MDM2 is frequently found amplified and overexpressed in a variety of human tumors...
  37. ncbi 5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction
    Xiao Xin Sun
    Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 282:8052-9. 2007
    ..Here we report that 5-FU treatment leads to p53 stabilization and activation by blocking MDM2 feedback inhibition through ribosomal proteins...
  38. pmc Specific domains of nucleolin interact with Hdm2 and antagonize Hdm2-mediated p53 ubiquitination
    Purvi Bhatt
    New York University School of Medicine, NY, USA
    FEBS J 279:370-83. 2012
    ..Earlier we reported that human nucleolin binds to the p53 antagonist human double minute 2 (Hdm2) as determined by reciprocal co-immunoprecipitation assays using cell lysates...
  39. ncbi Interaction between the retinoblastoma protein and the oncoprotein MDM2
    Z X Xiao
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 375:694-8. 1995
    ..The cellular oncoprotein, Mdm2, binds to and downmodulates p53 function; its human homologue, MDM2, is amplified in certain human tumours, ..
  40. doi FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53
    Anna Maria Ochocka
    Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Level 5, University of Dundee, Dundee DD1 9SY, United Kingdom
    FEBS Lett 583:621-6. 2009
    The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop...
  41. doi MDM2 SNP309 is associated with endometrial cancer susceptibility: a meta-analysis
    Yan Li
    Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, People s Republic of China
    Hum Cell 24:57-64. 2011
    Epidemiological studies have investigated the association between MDM2 promoter SNP 309 (T/G) and endometrial cancer susceptibility. However, the results are still controversial...
  42. pmc Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11
    Masato Sasaki
    Global Centers of Excellence Program, Akita University Graduate School of Medicine, Akita, Japan
    Nat Med 17:944-51. 2011
    ..Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1...
  43. ncbi Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2
    Erik Meulmeester
    Department of Molecular and Cell Biology, Leiden University Medical Center, P O Box 9503, 2300 RA Leiden, The Netherlands
    Mol Cell 18:565-76. 2005
    ..HAUSP also modulates p53 stability indirectly by deubiquitination and stabilization of Hdm2. The Hdmx protein affects p53 stability as well through its interaction with and regulation of Hdm2...
  44. ncbi The conformationally flexible S9-S10 linker region in the core domain of p53 contains a novel MDM2 binding site whose mutation increases ubiquitination of p53 in vivo
    Harumi Shimizu
    Department of Molecular and Cellular Pathology, The Cancer Research UK Laboratories, The University of Dundee, Dundee DD1 9SY, Scotland
    J Biol Chem 277:28446-58. 2002
    Although the N-terminal BOX-I domain of the tumor suppressor protein p53 contains the primary docking site for MDM2, previous studies demonstrated that RNA stabilizes the MDM2.p53 complex using a p53 mutant lacking the BOX-I motif...
  45. pmc Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway
    Yanping Zhang
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Mol Cell Biol 23:8902-12. 2003
    ..Here we report that the human homologue of MDM2, HDM2, binds to ribosomal protein L11. L11 binds a central region in HDM2 that is distinct from the ARF binding site...
  46. ncbi Dynamics of the p53-Mdm2 feedback loop in individual cells
    Galit Lahav
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Nat Genet 36:147-50. 2004
    ..We present a system for following, in individual living cells, the dynamics of p53 and its negative regulator Mdm2 (refs...
  47. pmc Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism
    Mu Shui Dai
    Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239
    J Biol Chem 281:24304-13. 2006
    Inhibition of the MDM2-p53 feedback loop is critical for p53 activation in response to cellular stresses...
  48. doi Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner
    B Mahata
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland
    Oncogene 31:3060-71. 2012
    ..We found that direct binding to Mdm2 E3 ligase and NEDDylation of L11 are critical regulators for L11 promoter recruitment...
  49. pmc Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress
    Sladana Bursac
    Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, 51000 Rijeka, Croatia
    Proc Natl Acad Sci U S A 109:20467-72. 2012
    ..The ability of ribosomal proteins L5, L11, L23, L26, or S7 to bind Mdm2 and inhibit its ubiquitin ligase activity has been suggested as a critical step in p53 activation under these ..
  50. ncbi The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53
    J Pomerantz
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Cell 92:713-23. 1998
    ..abrogated when p53 is neutralized by viral oncoproteins and dominant-negative mutants but not by the p53 antagonist MDM2. This finding, coupled with the observations that p19Arf and MDM2 physically interact and that p19Rrf blocks MDM2-..
  51. ncbi Identification of a cryptic nucleolar-localization signal in MDM2
    M A Lohrum
    NCI FCRDC, Building 560, Room 22 96, West 7th Street, Frederick, Maryland 21702 1201, USA
    Nat Cell Biol 2:179-81. 2000
  52. ncbi Defining the molecular basis of Arf and Hdm2 interactions
    B Bothner
    Department of Structural Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Mol Biol 314:263-77. 2001
    Understanding the interaction of Arf and Hdm2 has recently become a central issue in cancer biology...
  53. ncbi The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop
    Xiongbin Lu
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
    Cancer Cell 12:342-54. 2007
    ..One transcriptional target of p53 is Mdm2, an E3 ubiquitin ligase that interacts with p53 to promote its proteasomal degradation in a negative feedback ..
  54. doi Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling
    Xiaoliang L Xu
    Dyson Vision Research Institute, Weill Cornell Medical College, New York, NY 10021, USA
    Cell 137:1018-31. 2009
    ..We also demonstrate that human cone precursors prominently express MDM2 and N-Myc, that retinoblastoma cells require both of these proteins for proliferation and survival, and that MDM2 ..
  55. doi Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis
    Konstantinos P Economopoulos
    School of Medicine, National University of Athens, Athens, Greece
    Breast Cancer Res Treat 120:211-6. 2010
    b>MDM2 SNP309 is a single nucleotide T > G polymorphism present in intron 1 of the MDM2 gene. A variety of case-control studies have been published evaluating the association between MDM2 SNP309 and breast cancer risk...
  56. pmc Mdm2 deficiency suppresses MYCN-Driven neuroblastoma tumorigenesis in vivo
    Zaowen Chen
    Texas Children s Cancer Center and Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
    Neoplasia 11:753-62. 2009
    ..Amplification of the MYCN oncogene correlates with the most clinically aggressive form of the cancer, and MDM2, a primary inhibitor of the p53 tumor suppressor, is a direct transcriptional target of, and positively regulated ..
  57. pmc Perturbation of 60 S ribosomal biogenesis results in ribosomal protein L5- and L11-dependent p53 activation
    Xiao Xin Sun
    Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 285:25812-21. 2010
    ..Multiple ribosomal proteins, including L5, L11, L23, and S7, have been shown to bind to and inhibit MDM2, leading to p53 activation...
  58. doi MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation
    Francesco Galli
    Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy
    J Cell Sci 123:2423-33. 2010
    ..Here, we describe a new regulatory pathway for the DeltaNp63alpha protein. We found that MDM2 binds DeltaNp63alpha in the nucleus promoting its translocation to the cytoplasm...
  59. pmc The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes
    V Marechal
    Service de Microbiologie, Hopital Rothschild, Paris, France
    Mol Cell Biol 14:7414-20. 1994
    ....
  60. ncbi Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors
    Natalia Issaeva
    Microbiology and Tumor Biology Center, Karolinska Institutet, SE 171 77 Stockholm, Sweden
    Nat Med 10:1321-8. 2004
    ..RITA may serve as a lead compound for the development of an anticancer drug that targets tumors with wild-type p53...
  61. ncbi Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX
    Baoli Hu
    Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    Cancer Res 67:8810-7. 2007
    The p53 tumor suppressor plays a key role in protection against malignant transformation. MDM2 and MDMX are important regulators of the transcriptional activity and stability of p53 by binding to its NH(2) terminus...
  62. pmc Ubiquitination and degradation of mutant p53
    Natalia Lukashchuk
    The Beatson Institute for Cancer Research, Switchback Rd, Glasgow G61 1BD, United Kingdom
    Mol Cell Biol 27:8284-95. 2007
    ..While Mdm2 can drive the degradation of both mutant and wild-type p53, our data suggest that the ability of Mdm2 to function ..
  63. doi MdmX is a substrate for the deubiquitinating enzyme USP2a
    N Allende-Vega
    CR UK Cell Transformation Research Group, Division of Molecular Medicine, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
    Oncogene 29:432-41. 2010
    It has previously been shown that ubiquitin-specific protease 2a (USP2a) is a regulator of the Mdm2/p53 pathway. USP2a binds to Mdm2 and can deubiquitinate Mdm2 without reversing Mdm2-mediated p53 ubiquitination...
  64. pmc High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma
    Jane Carr-Wilkinson
    Department of Cellular Pathology, Northern Institute for Cancer Research, Royal Victoria Infirmary, Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, United Kingdom
    Clin Cancer Res 16:1108-18. 2010
    ..p53 mutations are rare in diagnostic neuroblastomas, but we have previously reported inactivation of the p53/MDM2/p14(ARF) pathway in 9 of 17 (53%) neuroblastoma cell lines established at relapse.
  65. pmc Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase
    Hiroyuki Inuzuka
    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 18:147-59. 2010
    b>Mdm2 is the major negative regulator of the p53 pathway...
  66. ncbi Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A
    Christoph R Müller
    Department of Tumour Biology, Rikshospitalet Radiumhospitalet Medical Center, Oslo, Norway
    Int J Cancer 121:199-205. 2007
    The MDM2-antagonist Nutlin 3A can efficiently induce apoptosis in osteosarcoma cell lines with amplified MDM2. However, Nutlin-based therapy could be even more important in more common sarcoma types where this aberration is frequent...
  67. ncbi MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case-control studies
    Zhibin Hu
    Laboratory of Reproductive Medicine, Institute of Toxicology, Cancer Research Center of Nanjing Medical University, Nanjing 210029, China
    Cancer Epidemiol Biomarkers Prev 16:2717-23. 2007
    Since the identification of a well-characterized functional polymorphism named SNP309 in MDM2, abundant studies were published in the last 2 years to evaluate the association between SNP309 and tumor risk in diverse populations...
  68. doi Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing
    Shiang Fu Huang
    Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Tao Yuan, Taiwan
    Oral Oncol 45:16-22. 2009
    The recently identified single nucleotide polymorphism in the MDM2 promoter (SNP 309) may contribute to the early onset of both sporadic and hereditary malignancies in patients with defective p53...
  69. ncbi Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein
    J E Landers
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104 6069, USA
    Cancer Res 57:3562-8. 1997
    The mdm2 oncogene has transforming potential that is activated by overexpression...
  70. ncbi Dual-site regulation of MDM2 E3-ubiquitin ligase activity
    Maura Wallace
    CRUK Interferon and Cell Signalling Group, University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, United Kingdom
    Mol Cell 23:251-63. 2006
    The control of p53 ubiquitination by MDM2 provides a model system to define how an E3-ligase functions on a conformationally flexible substrate...
  71. pmc Monoubiquitylation promotes mitochondrial p53 translocation
    Natasha D Marchenko
    Department of Pathology, Stony Brook University, Stony Brook, New York, NY 11794 869, USA
    EMBO J 26:923-34. 2007
    ..Using various manipulations that enhance or diminish p53 ubiquitylation, our data provide evidence that Mdm2-mediated monoubiquitylation of p53 greatly promotes its mitochondrial translocation and thus its direct ..
  72. ncbi MDM2 and p53 in childhood acute lymphoblastic leukemia: higher expression in childhood leukemias with poor prognosis compared to long-term survivors
    B Gustafsson
    Department of Paediatrics, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
    Pediatr Hematol Oncol 18:497-508. 2001
    In previous studies the authors have found increased expression of p53 and MDM2 proteins in leukemic cells in a majority of children eligible for bone marrow transplantation (BMT) due to relapse or prognostically unfavorable features...
  73. pmc MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells
    L Gu
    Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
    Oncogene 31:1342-53. 2012
    ..Here, we report that MYCN expression was regulated by the oncoprotein MDM2 at the post-transcriptional level and was associated with neuroblastoma cell growth...
  74. doi MDM2 is a useful prognostic biomarker for resectable gastric cancer
    Yang Ye
    Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China
    Cancer Sci 104:590-8. 2013
    Expression of MDM2 protein appears to be increased in malignancy and correlated to prognosis of tumors, but its role in gastric cancer remains controversial...
  75. pmc Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in tumorigenesis
    Tongsen Zheng
    1 Department of Pediatrics, Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey, New Brunswick, New Jersey 08903, USA 2 Key laboratory of Hepatosplenic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150086, China 3
    Nat Commun 4:2996. 2013
    ..The mechanism of mutp53 accumulation is poorly understood. Here we find that MDM2 isoforms promote mutp53 accumulation in tumours...
  76. ncbi MDM2 is a negative regulator of p21WAF1/CIP1, independent of p53
    Zhuo Zhang
    Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Biol Chem 279:16000-6. 2004
    The MDM2 oncogene has both p53-dependent and p53-independent activities. We have previously reported that antisense MDM2 inhibitors have significant anti-tumor activity in multiple human cancer models with various p53 statuses (Zhang, Z...
  77. ncbi The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53
    Hiroaki Higashitsuji
    Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo ku, Kyoto 606 8507, Japan
    Cancer Cell 8:75-87. 2005
    ..In vitro and in vivo experiments revealed that gankyrin binds to Mdm2, facilitating p53-Mdm2 binding, and increases ubiquitylation and degradation of p53...
  78. pmc Regulation of XIAP translation and induction by MDM2 following irradiation
    Lubing Gu
    Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Emory University School of Medicine, Atlanta, GA 30322, USA
    Cancer Cell 15:363-75. 2009
    ..Herein we demonstrate that the upregulation of XIAP protein levels is regulated by MDM2 at the translational level...
  79. pmc p38 phosphorylates Rb on Ser567 by a novel, cell cycle-independent mechanism that triggers Rb-Hdm2 interaction and apoptosis
    R B Delston
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA
    Oncogene 30:588-99. 2011
    ..by p38, but not Cdks, triggers an interaction between Rb and the human homolog of murine double minute 2 (Hdm2), leading to degradation of Rb, release of E2F1 and cell death...
  80. pmc HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replication
    Taisuke Izumi
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8507, Japan
    Proc Natl Acad Sci U S A 107:20798-803. 2010
    ..Vif enhances the stability and transcriptional activity of TP53 by blocking the MDM2-mediated ubiquitination and nuclear export of TP53...
  81. pmc Interplay between ribosomal protein S27a and MDM2 protein in p53 activation in response to ribosomal stress
    Xiao Xin Sun
    Department of Molecular and Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Biol Chem 286:22730-41. 2011
    ..Several ribosomal proteins have been shown to induce and activate p53 via inhibition of MDM2. Here, we report that S27a, a small subunit ribosomal protein synthesized as an 80-amino acid ubiquitin C-terminal ..
  82. doi Reciprocal repression between P53 and TCTP
    Robert Amson
    Centre National de la Recherche Scientifique Unité Mixte de Recherche 8113, Laboratoire de Biotechnologie et Pharmacologie Genetique Appliquee, Ecole Normale Superieure, Cachan, France
    Nat Med 18:91-9. 2011
    ..TCTP promotes P53 degradation by competing with NUMB for binding to P53-MDM2-containing complexes...
  83. doi A 40-bp insertion/deletion polymorphism in the constitutive promoter of MDM2 confers risk for hepatocellular carcinoma in a Chinese population
    Dong Dong
    Department of Forensic Medicine, Medical College of Soochow University, Suzhou, 215123, Jiangsu, China
    Gene 497:66-70. 2012
    ..the possible association between a 40-bp insertion/deletion polymorphism (indel) at constitutive promoter of MDM2 and risk of hepatocellular carcinoma (HCC) in a Chinese population...
  84. pmc Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population
    Cong Huang
    State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China
    Asian J Androl 14:691-4. 2012
    The TP53, a transcriptional regulator and tumor suppressor, is functionally important in spermatogenesis. MDM2 is a key regulator of the p53 pathway and modulates p53 activity...
  85. ncbi Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein
    D A Sharp
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6069, USA
    J Biol Chem 274:38189-96. 1999
    The MDM2 oncoprotein has transforming potential that can be activated by overexpression, and it represents a critical regulator of the p53 tumor suppressor protein...
  86. ncbi Function and dysfunction of the human oncoprotein MDM2
    Swati Palit Deb
    Department of Biochemistry and Molecular Biophysics and the Massey Cancer Center, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA
    Front Biosci 7:d235-43. 2002
    The protein MDM2 coded by the human homologue of mouse double minute-2 (mdm2) gene frequently overexpresses in malignant human breast and other tumors...
  87. pmc MDM2 promotes ubiquitination and degradation of MDMX
    Yu Pan
    Molecular Oncology Program, H Lee Moffitt Comprehensive Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA
    Mol Cell Biol 23:5113-21. 2003
    The p53 tumor suppressor is regulated by MDM2-mediated ubiquitination and degradation. Mitogenic signals activate p53 by induction of ARF expression, which inhibits p53 ubiquitination by MDM2...
  88. pmc Combined effects of p53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis B virus-related hepatocellular carcinoma
    Yun Yang
    The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
    Protein Cell 4:71-81. 2013
    ..Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the ..
  89. ncbi No association of MDM2 T309G polymorphism with susceptibility to Korean gastric cancer patients
    Y G Cho
    Department of Pathology, College of Medicine, Catholic University of Korea, Seoul, Korea
    Neoplasma 55:256-60. 2008
    Mouse double minute 2 (Mdm2) acts as a negative regulator of p53 by binding to the amino-terminus of p53...
  90. pmc BH3 activation blocks Hdmx suppression of apoptosis and cooperates with Nutlin to induce cell death
    Mark Wade
    Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell Cycle 7:1973-82. 2008
    ..We previously showed that Hdmx modulates tumor cell sensitivity to Nutlin-3a, a potent antagonist of the p53/Hdm2 interaction. In this report, we demonstrate that this also applies to MI-219, another Hdm2 antagonist...
  91. pmc MDM2 protein-mediated ubiquitination of numb protein: identification of a second physiological substrate of MDM2 that employs a dual-site docking mechanism
    Matylda Sczaniecka
    The Roslin Institute and Royal Dick School of Veterinary Science, University of Edinburgh, Easter Bush EH25 9RG, United Kingdom
    J Biol Chem 287:14052-68. 2012
    The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2...
  92. pmc The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity
    Masha V Poyurovsky
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    EMBO J 26:90-101. 2007
    b>Mdm2, a key negative regulator of the p53 tumor suppressor, is a RING-type E3 ubiquitin ligase...
  93. pmc p53 Arg72Pro and MDM2 T309G polymorphisms, histology, and esophageal cancer prognosis
    David W Cescon
    Department of Medical Biophysics, Princess Margaret Hospital, University of Toronto, Canada
    Clin Cancer Res 15:3103-9. 2009
    ..significance of two functional single nucleotide polymorphisms (SNP) in the p53 pathway (p53 Arg72Pro and MDM2 T309G) in patients with esophageal cancer, and to determine the importance of histologic subtype in the SNP-outcome ..
  94. pmc ATM-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53R2 protein against MDM2 to DNA damage
    Lufen Chang
    Department of Clinical and Molecular Pharmacology, City of Hope National Medical Center, Duarte, CA 91010 3000, USA
    Proc Natl Acad Sci U S A 105:18519-24. 2008
    ..b>MDM2, a ubiquitin ligase for p53, interacts and facilitates ubiquitination of the S72A-p53R2 mutant more efficiently ..
  95. pmc MDMX regulation of p53 response to ribosomal stress
    Daniele M Gilkes
    Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
    EMBO J 25:5614-25. 2006
    ..as disruption of rRNA biogenesis activates p53 by release of ribosomal proteins from the nucleoli, which bind to MDM2 and inhibit p53 degradation...
  96. pmc Quantitative analyses reveal the importance of regulated Hdmx degradation for p53 activation
    Yunyuan V Wang
    Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:12365-70. 2007
    ..Hdm2 and Hdmx are critical negative regulators of P53 because Hdm2 regulates P53 abundance, and both can antagonize P53 ..
  97. pmc A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus
    L D Mayo
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Proc Natl Acad Sci U S A 98:11598-603. 2001
    The Mdm2 oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumor suppressor protein. To regulate p53, Mdm2 must gain nuclear entry, and the mechanism that induces this is now identified...
  98. pmc Mdm2 promotes genetic instability and transformation independent of p53
    Alyssa Bouska
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Mol Cell Biol 28:4862-74. 2008
    b>Mdm2, a regulator of the tumor suppressor p53, is frequently overexpressed in human malignancies. Mdm2 also has unresolved, p53-independent functions that contribute to tumorigenesis...
  99. pmc CBP and p300 are cytoplasmic E4 polyubiquitin ligases for p53
    Dingding Shi
    Department of Cancer Biology, University of Massachusetts Medical School and University of Massachusetts Memorial Cancer Center, 364 Plantation Street, Worcester, MA 01605, USA
    Proc Natl Acad Sci U S A 106:16275-80. 2009
    ....
  100. pmc JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress
    Juhong Liu
    Gene Regulation Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA
    EMBO J 30:846-58. 2011
    ..The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress...
  101. doi 5-Aza-2'-deoxycytidine reactivates gene expression via degradation of pRb pocket proteins
    Zhixing Zheng
    Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China
    FASEB J 26:449-59. 2012
    ..Mouse double minute 2 (MDM2) played a critical role in this 5-aza-CdR-induced degradation of pRb...

Research Grants76

  1. Regulation of Mdm2 compartmentalization
    Lindsey Mayo; Fiscal Year: 2009
    ..mitogens such as IGF-1 and EGF-1 signal to activate the oncogenic activity of the murine double minute protein (Mdm2). Mdm2 plays a role in tumorigenesis in part through the disruption of the tumor suppressor protein p53...
  2. Mechanisms of Mdm2/Mdmx in repressing p53
    Wei Gu; Fiscal Year: 2013
    ..Activation of p53 function is crucial for suppressing tumor growth in many tumor types. It is well accepted that Mdm2 and its related protein Mdmx (also called Mdm4) play a major part in the scope of negatively regulating the tumor ..
  3. KAREN ELIZABETH POLLOK; Fiscal Year: 2014
    ..In this proposal, we will investigate the efficacy of a novel combination therapy that targets the HDM2/p53 network and DNA repair...
  4. Amato J Giaccia; Fiscal Year: 2014
    ..Hypoxia-induced p53 is nuclear and associates with p53-response elements in target genes, such as mdm2 and p21...
  5. Zhenkun Lou; Fiscal Year: 2015
    ..Among them, Mdm2-induced ubiquitination of p53 induces p53 nuclear export and degradation, which is a major cellular mechanism that ..
  6. Molecular Mechanism of Mule in DNA Damage Response and Tumorigenesis
    Qing Zhong; Fiscal Year: 2013
    ..Ubiquitin chain formation, E3 activity (Mule versus Mdm2), the contribution of Mcl-1 and p53 in Mule-dependent DNA damage response, and regulatory mechanisms of Mcl-1 and ..
  7. Michael B Kastan; Fiscal Year: 2016
    ..p53 protein, primarily via modulation of proteasome-mediated degradation of p53 protein by the E3-ubiquitin ligase, Hdm2. However, support from this grant in the previous funding period allowed us to demonstrate that increased ..
  8. PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
    Nelson Fausto; Fiscal Year: 2010
    ..lack of p53 protein expression is caused by post-translational mechanisms that destabilize p53 through increased Mdm2 binding and proteasomal degradation...
  9. Regulation of the ATM/ATR-p53 DNA Damage Signaling Pathway by the Wip1 Phosphatas
    Xiongbin Lu; Fiscal Year: 2013
    ..provided by applicant): Negatively regulated by controlled degradation through its antagonists including Mdm2, Mdm4 and COP1, the tumor suppressor p53 have a high turn-around rate and low physiological levels...
  10. Role of p53 in cell cycle checkpoints
    James J Manfredi; Fiscal Year: 2013
    ..These include novel roles for Mdm2 in affecting the ability of p21CIP1 to inhibit cyclin-dependent kinases and in regulating Cdc25C protein stability...
  11. Regulation of tumorigenic spliced isoforms in cancer
    Aixa Tapia Santos; Fiscal Year: 2010
    ..The Murine Double Minute 2 (MDM2) protein negatively regulates the tumor suppressor protein p53 and its over expression results in transformation of ..
  12. Functional analysis of a putative ATM/ATR substrate RFWD3
    Yi Wang; Fiscal Year: 2012
    ..At least five ubiquitin ligases (E6-AP, HDM2, ARF-BP1, COP1, and PIRH2) and an ubiquitin-specific protease (HAUSP) that opposes the ligases have been identified ..
  13. Identification of Novel Protein Phosphatases in the ATM Signaling Pathway
    Xiongbin Lu; Fiscal Year: 2010
    ..In particular, Wip1 stabilizes Mdm2 and MdmX by dephosphorylating their ATM phosphorylation site, resulting in decreased levels and activity of p53...
  14. Oncogenic Function of a P53-Induced Phosphatase
    Lawrence A Donehower; Fiscal Year: 2012
    ..structurally intact p53, p53 signaling is often activated through altered expression of p53 regulators, such as Mdm2 or ARF...
  15. Wenyi Wei; Fiscal Year: 2015
    ..b>Mdm2 is the major negative regulator of p53 and frequently overexpressed in tumors, yet the underlying mechanisms are ..
  16. Wenyi Wei; Fiscal Year: 2016
    ..Lastly, our proposal explores how Cdh1 itself is regulated. Our preliminary data indicated that the Mdm2 oncoprotein controls the stability of Cdh1 in late G1/S phase...
  17. Regulation of p53 function by Daxx
    Xiaolu Yang; Fiscal Year: 2012
    ..In unstressed cells, the potent anti-proliferative effects of p53 are restrained by Mdm2, a ubiquitin ligase (E3) that promotes rapid p53 ubiquitination and degradation...
  18. Defective p53 synthesis following DNA damage and cancer development
    Da Qing Yang; Fiscal Year: 2011
    ..is widely accepted that the accumulation of p53 is regulated by protein stabilization through its interaction with MDM2 protein, there is clear evidence indicating that increased synthesis of p53 in response to DNA damage also ..
  19. David Wald; Fiscal Year: 2014
    ..A critical cell cycle checkpoint regulator is the p53 tumor suppressor, which is kept in check in normal cells by HdmX and Hdm2...
  20. Melissa A Kacena; Fiscal Year: 2015
    ..with MKs, the expression of the cell cycle arrest protein Retinoblastoma (Rb), and murine double minute-2 (Mdm2), an E3 ubiquitin ligase that regulates proteosome mediated degradation, are transiently decreased...
  21. Model systems for hematologic disorders caused by ribosomal protein deficiency
    George Thomas; Fiscal Year: 2010
    ..in the production of rps, leading to cell- cycle arrest due to the binding and inhibition of human double minute 2 (HDM2) by 60S rpL11 and rpL5...
  22. MODELING AND RESCUE OF DBA IN THE MOUSE
    Philip J Mason; Fiscal Year: 2010
    ..that DBA is caused by disrupted ribosome biogenesis causing an imbalance of ribosomal proteins that, by inhibiting MDM2, causes an activation of the p53 pathway that is detrimental to the maturing red cells...
  23. The in vivo role of the mitochondrial p53 cell death program
    UTE MARTHA MOLL; Fiscal Year: 2013
    ..5) As to the mechanism of translocation, monoubiquitylation by Mdm2-type E3 ligases promotes mitochondrial p53 translocation...
  24. TERMINAL DIFFERENTIATION OF THE RENAL EPITHELIUM
    Samir S El-Dahr; Fiscal Year: 2012
    ..vivo genetic and biochemical approaches, together with an in vitro organ culture system, to test a model in which Mdm2 and other negative regulators of p53 exert strict spatiotemporal control on p53 during terminal nephron ..
  25. EBNA3C and tumor supressors
    Erle S Robertson; Fiscal Year: 2010
    ..of p53 through the regulatory functions of EBNA3C, which can lead stabilization of p53 and suppression of Mdm2 activity which allows for cell proliferation and cell cycle regulation in EBV transformed cells...
  26. Repair of oxidative DNA damage in mammalian cells
    Tadahide Izumi; Fiscal Year: 2013
    ..We have discovered that APE1 is ubiquitinated by mouse double minute 2 (MDM2), and that the ubiquitination is induced by genotoxic stress in a p53-dependent manner...
  27. Investigation of a novel regulator of Myc-driven tumorigenesis
    Mark W Gramling; Fiscal Year: 2012
    ..Data indicate that Mdm2 binding protein (MTBP), a novel protein with unknown function, does not influence Mdm2 as its name would suggest, ..
  28. George Thomas; Fiscal Year: 2015
    ..there is an upregulation of p53 mediated by the binding of the 60S rps, rpL5 and rpL11, to human double minute 2 (MDM2 or Hdm2), leads to G1 cell-cycle arrest...
  29. Rebecca Page; Fiscal Year: 2016
    ..It also controls cell death in response to cellular stresses through the post-translational modification of p53 and MDM2 and it plays essential role in the regulation of the retinoblastoma protein in response to cellular stress, ..
  30. Ravi Bhatia; Fiscal Year: 2016
    ..In addition, activation of p53 by direct targeting of HDM2, a well characterized regulator of p53 expression, could also be useful for targeting CML LSC...
  31. Joaquin M Espinosa; Fiscal Year: 2016
    ..in the TP53 gene, and in the remaining fraction p53 is likely attenuated by hyperactivation of repressors such as MDM2. Activated p53 participates in various cellular responses to stress including cell cycle arrest and apoptosis...
  32. Dmp1-p53/YY1 interplays and their roles in lung cancer development
    Guangchao Sui; Fiscal Year: 2013
    ..We hypothesize that Dmp1 directly binds to p53 and competes with Mdm2-mediated ubiquitination, nuclear export, and inhibition of transcription of p53...
  33. Christine M Eischen; Fiscal Year: 2015
    ..b>Mdm2 (Two) Binding Protein (MTBP) was identified in a yeast-two-hybrid as a protein that bound to Mdm2, a regulator of ..
  34. Steven R Grossman; Fiscal Year: 2014
    ..p53 is monoubiquitinated by the E3 ligase MDM2, and work from the prior grant has shown that the p300/CBP coactivators are E4 enzymes catalyzing further ..
  35. The Sixth International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2011
    ..Indeed, a majority of human tumors have sustained missense mutation in the TP53 gene. Mdm2 is a negative regulator of p53 that has been shown to act by inhibiting the transcriptional activity of p53 via ..
  36. COG studies of gene amplification in rhabdomyosarcoma
    FREDERIC BARR; Fiscal Year: 2009
    ..amplification in 26% of cases and revealed two distinct amplicons, one including CDK4 and another including MDM2. Comparison with gene expression indicated that CDK4 but not MDM2 amplification results in overexpression...
  37. Carol Prives; Fiscal Year: 2016
    ..It is equally imperative to elucidate how its negative regulators, Mdm2 and MdmX function to restrain p53...
  38. In vivo function of Mdm2 E3 ubiquitin ligase
    Yanping Zhang; Fiscal Year: 2013
    ..the p53 gene that compromise p53 functions occur in 50% of human cancers, and elevated levels of two p53 inhibitors Mdm2 and Mdm4 occur in most of the rest...
  39. The Seventh International Mdm2 Workshop
    James J Manfredi; Fiscal Year: 2013
    ..Indeed, a majority of human tumors have sustained missense mutation in the TP53 gene. Mdm2 is a negative regulator of p53 that has been shown to act by inhibiting the transcriptional activity of p53 via ..
  40. Chunhong Yan; Fiscal Year: 2015
    ..activity of p53, and also discover a link of ATF3 with other p53 network proteins including E3 ubiquitin ligase MDM2 and histone acetyltransferases p300, Tip60 and hMOF...
  41. Clodagh O'Shea; Fiscal Year: 2016
    ..transcription is suppressed in ONYX-015 infected cells, even upon treatment with adriamycin, irradiation or Mdm2 antagonists...
  42. Wei Gu; Fiscal Year: 2016
    ..2011;Zhang and Lu, 2009). It is well accepted that Mdm2 and its related protein Mdmx (also called Mdm4) play a major part in the scope of specifically inhibiting p53 ..
  43. MOLECULAR DYNAMICS IN CELLULAR AGING: A SYNTHETIC BIOLOGY APPROACH.
    CLIFFORD LEE WANG; Fiscal Year: 2012
    ..P53 is regulated by a negative feedback loop;it is a transcriptional activator for its own negative regulator, Mdm2. As a result, p53 levels undergo oscillations for an extended period after DNA damage...
  44. MUSHUI DAI; Fiscal Year: 2016
    ..b>MDM2, a RING-finger ubiquitin E3 ligase, plays a major role in the regulation of p53 levels...
  45. Dawn S Chandler; Fiscal Year: 2014
    ..we have shown that specific types of cell stress initiate coordinated alternative splicing of the p53 modulators mdm2 and mdm4 (mdmx)...
  46. Pradip Raychaudhuri; Fiscal Year: 2014
    ..How does DDB2 overcome the apoptosis-inhibitory activity of Mdm2? PUBLIC HEALTH RELEVANCE: Project Narrative Public Health Relevance: DDB2 was identified as the product of the XP-E ..
  47. p53-independent function of Mdmx in tumorigenesis
    ALEXIA NATTASHA MELO; Fiscal Year: 2013
    ..This project will investigate a specific oncoprotein, Mdmx, that is an Mdm2 family member, and its role in lymphoma development...
  48. In vivo function and mechanism of the r-protein-Mdm2-p53 pathway
    Yanping Zhang; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): In vivo function and mechanism of the r-protein-Mdm2-p53 pathway Mdm2 interacts with a large number of proteins and plays a critical role in regulating cell growth, proliferation and apoptosis...
  49. Jiandong Chen; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): MDM2 and its homolog MDMX are important regulators of the p53 tumor suppressor. Knockout experiments showed that both are essential for viability of mouse embryos...
  50. Dissecting E2f3's role in tumorigenesis
    Jacqueline A Lees; Fiscal Year: 2010
    ..is dependent upon the inactivation of two key tumor suppressor pathways, p16- cycD/cdk4-pRB-E2F and p19Arf-mdm2-p53, that together regulate cellular proliferation and the tumor surveillance response...
  51. Yanping Zhang; Fiscal Year: 2016
    ..Canonically, the primary negative regulator of the TP53 protein product p53, Mdm2, is considered to regulate p53 through two mechanisms;1) through direct binding to the p53 transactivation domain, ..
  52. SARA MARIE FRANCIS-REED; Fiscal Year: 2014
    ..My thesis laboratory discovered a new activator of p53 signaling called NIAM (Nuclear Interactor of ARF and Mdm2)...
  53. Guillermina Lozano; Fiscal Year: 2016
    ..Additionally, over-expression of MDM2 and MDM4 which encode p53 inhibitors are also common events in tumorigenesis and contribute to inactivation of the ..
  54. Gary W Daughdrill; Fiscal Year: 2016
    ..We recently identified multiple novel ATM phosphorylation sites near the RING domain of MDM2, an E3 ligase that promotes p53 ubiquitination...
  55. Fred Bunz; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): This project seeks to determine whether polymorphisms in the TP53 and MDM2 genes are responsible for early-onset breast and colon cancer in African Americans...
  56. Role of MDM2 in Cell Proliferation and Tumorigenesis
    Zhi Xiong Jim Xiao; Fiscal Year: 2010
    ..How Rb is degraded is poorly understood. Work from us and others demonstrates that the cellular oncoprotein MDM2 also targets and promotes Rb protein degradation...
  57. Stephen Jones; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Mdm2 and MdmX (also known as Mdm4) are key regulators of the p53 tumor suppressor...
  58. Xinbin Chen; Fiscal Year: 2014
    ..studies showed that the stability of PolH protein is decreased upon DNA damage and PolH physically interacts with Mdm2 and Pirh2, both of which are a p53 target gene and an E3 ligase...
  59. Development of Protein Surface Binding, Low Entropy Oligomers
    Christian E Schafmeister; Fiscal Year: 2013
    ..We will test the hypothesis on three target proteins: hDMX, HIV gp41 and the seven-transmembrane bound G-protein coupled receptor GLP-1R...
  60. Stochastic dynamics for multiscale biology
    Eric D Mjolsness; Fiscal Year: 2011
    ..DNA damage sensing (through ATM) and repair control (though p53 and Mdm2) are at least equally important to cancer research owing to the central role that failure of these systems play in ..
  61. The Role of MDM Proteins in Cell Growth and Tumorigenesis
    Stephen Jones; Fiscal Year: 2009
    Project Summary / Abstract Mdm2 and MdmX (also known as Mdm4) are key regulators of the p53 tumor suppressor...
  62. Cellular Responses to p53 Activation by Nutlin-3a
    Carl G Maki; Fiscal Year: 2013
    ..of the Nutlin-3 (Nutlin), a small molecule that activates wild-type p53 by blocking its interaction with MDM2, the primary negative regulator of p53 activity in cells...
  63. Ribosomal Protein Gene Silencing in Neural Crest Stem Cells
    JOHNSON MING YU LIU; Fiscal Year: 2010
    ..Rpl5 and Rpl11 bind cooperatively, possibly with 5S rRNA, to the murine double minute (Mdm2) protein, a critical negative regulator of the p53 tumor suppressor...
  64. Study on the intracellular Network of TBX3
    Taosheng Huang; Fiscal Year: 2010
    ..TBX3 can also inhibit the expression of the p14ARF gene, a tumor suppressor and an inhibitor of MDM2-mediated degradation of p53. Therefore, overexpression of TBX3 decreases the stability of p53...
  65. Carol Prives; Fiscal Year: 2015
    ..Additionally Lowe will study the impact of reactivation of latent p53 by down-regulation of Mdm2, as well as perform an shRNA screen to identify genes whose inhibition facilitates death of mutant-p53 dependent ..
  66. MYC ONCOPROTEIN FUNCTION
    ROBERT NEIL EISENMAN; Fiscal Year: 2013
    ..We will identify myc-cooperating genes under conditions of increased sensitivity to apoptosis (i.e. mdm2 hypomorphic mutant mice) or under conditions where myc function is no longer antagonized by Mad proteins (i.e...
  67. Development of sd-rxRNAs as Therapy for Retinoblastoma and Other Malignancies
    Pamela Pavco; Fiscal Year: 2012
    ..This normal circuitry includes extremely high expression of murine double minute oncogene (MDM2), V-myc myelocytomatosis viral related oncogene (MYCN), thyroid hormone receptor [unreadable]2 (THRB2) and retinoic ..
  68. Biomarker Models of Prostate Cancer Outcome After Radiotherapy
    Alan Pollack; Fiscal Year: 2010
    ..proteins related to apoptosis and the cell cycle, and have found 7 prostate cancer tissue biomarkers (Ki-67, p53, MDM2, bcl-2, bax, p16 and cox-2) measured using immunohistochemistry (IHC) that are predictive of outcome in patients ..
  69. TRANSLATIONAL CONTROL OF ONCOPROTEIN MDM2 SYNTHESIS
    David Morris; Fiscal Year: 2003
    b>Oncoprotein MDM2 is a component of a negative feedback loop that regulates the activity and cellular level of tumor suppressor p53...
  70. Differential regulation of cardiomyocyte survival and hypertrophy
    Peter Erhardt; Fiscal Year: 2010
    The overall goal of this application is to investigate the role of Mdm2 and its homolog Mdm4 in maladaptive cardiac hypertrophy and the associated apoptosis...
  71. STRUCTURE AND FUNCTION OF SV40 NON-VIRION PROTEINS
    David Livingston; Fiscal Year: 2007
    ..whether the E3B4 ubiquitin ligase function of p300/CBP represents a useful anti-cancer therapeutic target in MDM2 overexpressing human tumor cells and 4) to decipher the biochemical functions of TRRAP and p400 and to determine ..
  72. ARF MDM2 P53 TUMOR SUPPRESSION PATHWAY
    Yanping Zhang; Fiscal Year: 2005
    ..oncogene- activated hyperproliferative checkpoint pathway through binding to and antagonizing the nuclear export of MDM2, thereby preventing cytoplasmic degradation of p53...
  73. PROTEOLYTIC CLEAVAGE OF MDM2 DURING APOPTOSIS
    Jiandong Chen; Fiscal Year: 2000
    DESCRIPTION: (adapted from the investigator's abstract) The mdm2 oncogene encodes a 90 kDa protein that binds to the p53 tumor suppressor protein and negatively regulates its function in transcription, cell cycle arrest and programmed ..
  74. MOLECULAR MECHANISM OF CHEMOPREVENTION BY APIGENIN
    Jill Pelling; Fiscal Year: 2004
    ..Interestingly, the applicant did not observe any increased accumulation of MDM2 protein in apigenin-treated cells, which is unexpected considering that the MDM2 gene is a downstream target of p53 ..
  75. MOLECULAR MECHANISM OF MDM2 INHIBITION OF MYOGENESIS
    Mark Vossler; Fiscal Year: 2001
    ..This lesion is the amplification of the MDM2 locus from chromosome 12 translocated to chromosome 14...
  76. The Structure and Function of S100 Proteins
    DAVID JOSEPH WEBER; Fiscal Year: 2010
    ..malignant melanoma;(ii) S100B down-regulates p53 protein levels and its tumor suppression function via promoting hdm2-dependent ubiquitination/degradation of p53;(iii) like hdm2, the S100B promoter is activated by p53 as part of a ..