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
Products:     MDM2

Top Publications

  1. Ezzikouri S, Essaid El Feydi A, Afifi R, Benazzouz M, Hassar M, Pineau P, et al. Impact of TP53 codon 72 and MDM2 promoter 309 allelic dosage in a Moroccan population with hepatocellular carcinoma. Int J Biol Markers. 2011;26:229-33 pubmed publisher
    Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53 gene (rs1042522) and in the promoter region of the MDM2 gene (SNP309; rs2279744) have been shown to play a role in the predisposition to many cancers...
  2. Xu X, Fang Y, Lee T, Forrest D, Gregory Evans C, Almeida D, et al. Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling. Cell. 2009;137:1018-31 pubmed publisher
    ..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 ..
  3. Zhang X, Wang W, Wang H, Wang M, Xu W, Zhang R. Identification of ribosomal protein S25 (RPS25)-MDM2-p53 regulatory feedback loop. Oncogene. 2013;32:2782-91 pubmed publisher
    There is an increasing interest in determining the role of ribosomal proteins (RPs) in the regulation of MDM2-p53 pathway in coordinating cellular response to stress...
  4. Bernal F, Wade M, Godes M, Davis T, Whitehead D, Kung A, et al. A stapled p53 helix overcomes HDMX-mediated suppression of p53. Cancer Cell. 2010;18:411-22 pubmed publisher
    ..However, the efficacy of HDM2 inhibition can be compromised by overexpression of HDMX, an HDM2 homolog that binds and sequesters p53...
  5. Wu H, Pomeroy S, Ferreira M, Teider N, Mariani J, Nakayama K, et al. UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. Nat Med. 2011;17:347-55 pubmed publisher
    ..We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice)...
  6. Ryan B, Calhoun K, Pine S, Bowman E, Robles A, Ambs S, et al. MDM2 SNP285 does not antagonize the effect of SNP309 in lung cancer. Int J Cancer. 2012;131:2710-6 pubmed publisher
    Conflicting reports exist regarding the contribution of SNP309 in MDM2 to cancer risk. Recently, SNP285 was shown to act as an antagonist to SNP309 by overriding the effect of SNP309 on SP1-mediated transcription...
  7. Piotrowski P, Lianeri M, Rubis B, Knuła H, Rybczynska M, Grodecka Gazdecka S, et al. Murine double minute clone 2,309T/G and 285G/C promoter single nucleotide polymorphism as a risk factor for breast cancer: a Polish experience. Int J Biol Markers. 2012;27:e105-10 pubmed publisher
    ..Recently, a functional polymorphism, MDM2 285G>C (rs117039649), has been discovered...
  8. Sczaniecka M, Gladstone K, Pettersson S, McLaren L, Huart A, Wallace M. MDM2 protein-mediated ubiquitination of numb protein: identification of a second physiological substrate of MDM2 that employs a dual-site docking mechanism. J Biol Chem. 2012;287:14052-68 pubmed publisher
    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...
  9. Yoneda T, Kuboyama A, Kato K, Ohgami T, Okamoto K, Saito T, et al. Association of MDM2 SNP309 and TP53 Arg72Pro polymorphisms with risk of endometrial cancer. Oncol Rep. 2013;30:25-34 pubmed publisher
    ..We have previously shown that the ER/MDM2/p53/p21 pathway plays an important role in endometrial carcinogenesis...

More Information

Publications204 found, 100 shown here

  1. Tuna G, Kucukhuseyin O, Arikan S, Kaytan Sağlam E, Guler E, Cacina C, et al. Do CDKN2 p16 540 C>G, CDKN2 p16 580 C>T, and MDM2 SNP309 T>G gene variants act on colorectal cancer development or progression?. DNA Cell Biol. 2013;32:400-8 pubmed publisher
    ..G1/S transition by regulating the p53 pathway, which was regulated by a nuclear oncoprotein, mouse double minute 2 (MDM2)...
  2. Jacob A, O BRIEN D, Singh R, Comiskey D, Littleton R, Mohammad F, et al. Stress-induced isoforms of MDM2 and MDM4 correlate with high-grade disease and an altered splicing network in pediatric rhabdomyosarcoma. Neoplasia. 2013;15:1049-63 pubmed
    ..panel of 70 RMS tumors has identified specific alternative splice variants of the oncogenes Murine Double Minute 2 (MDM2) and MDM4 as potential biomarkers for RMS...
  3. Sloan K, Bohnsack M, Watkins N. The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress. Cell Rep. 2013;5:237-47 pubmed publisher
    ..a major consumer of cellular energy, and defects result in p53 activation via repression of mouse double minute 2 (MDM2) homolog by the ribosomal proteins RPL5 and RPL11...
  4. Kaindl U, Morak M, Portsmouth C, Mecklenbräuker A, Kauer M, Zeginigg M, et al. Blocking ETV6/RUNX1-induced MDM2 overexpression by Nutlin-3 reactivates p53 signaling in childhood leukemia. Leukemia. 2014;28:600-8 pubmed publisher
    ..perceived p53 pathway alterations in model cell lines and primary leukemias and, in particular, how E/R upregulates MDM2, the predominant negative regulator of p53...
  5. Peng Q, Lao X, Chen Z, Lai H, Deng Y, Wang J, et al. TP53 and MDM2 gene polymorphisms, gene-gene interaction, and hepatocellular carcinoma risk: evidence from an updated meta-analysis. PLoS ONE. 2013;8:e82773 pubmed publisher
    The association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent...
  6. Pan X, Li Y, Feng J, Wang X, Hao B, Shi R, et al. A functional polymorphism T309G in MDM2 gene promoter, intensified by Helicobacter pylori lipopolysaccharide, is associated with both an increased susceptibility and poor prognosis of gastric carcinoma in Chinese patients. BMC Cancer. 2013;13:126 pubmed publisher
    Studies on the association between MDM2 SNP309 (T > G) and gastric cancer have reported conflicting results...
  7. Chang Y, Graves B, Guerlavais V, Tovar C, Packman K, To K, et al. Stapled ?-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proc Natl Acad Sci U S A. 2013;110:E3445-54 pubmed publisher
    ..Here, we report a potent and selective dual inhibitor of MDM2 and MDMX, ATSP-7041, which effectively activates the p53 pathway in tumors in vitro and in vivo...
  8. Zheng T, Wang J, Zhao Y, Zhang C, Lin M, Wang X, et al. Spliced MDM2 isoforms promote mutant p53 accumulation and gain-of-function in tumorigenesis. Nat Commun. 2013;4:2996 pubmed publisher
    ..The mechanism of mutp53 accumulation is poorly understood. Here we find that MDM2 isoforms promote mutp53 accumulation in tumours...
  9. Chen J, Zhu B, Chen J, Li Y. Genetic variations in MDM2 and P53 genes confer risk for adult acute lymphoblastic leukemia in a Chinese population. DNA Cell Biol. 2013;32:414-9 pubmed publisher
    The tumor suppressor P53 and its negative regulator mouse double minute 2 (MDM2) play crucial roles in carcinogenesis...
  10. Sparks A, Dayal S, Das J, Robertson P, Menendez S, Saville M. The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a. Oncogene. 2014;33:4685-96 pubmed publisher
    p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation...
  11. Zhao Y, Yu H, Hu W. The regulation of MDM2 oncogene and its impact on human cancers. Acta Biochim Biophys Sin (Shanghai). 2014;46:180-9 pubmed publisher
    ..The levels and activity of p53 is under tight regulation to ensure its proper function. Murine double minute 2 (MDM2), a p53 target gene, is an E3 ubiquitin ligase...
  12. Joo H, Kim J, Jeong J, Seong K, Nam S, Yang K, et al. Ret finger protein 2 enhances ionizing radiation-induced apoptosis via degradation of AKT and MDM2. Eur J Cell Biol. 2011;90:420-31 pubmed publisher
    ..Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT...
  13. Jin Y, Zeng S, Lee H, Lu H. MDM2 mediates p300/CREB-binding protein-associated factor ubiquitination and degradation. J Biol Chem. 2004;279:20035-43 pubmed
    We recently reported that MDM2, a negative feedback regulator of the tumor suppressor p53, inhibits p300/CREB-binding protein-associated factor (PCAF)-mediated p53 acetylation...
  14. Sui G, Affar E, Shi Y, Brignone C, Wall N, Yin P, et al. Yin Yang 1 is a negative regulator of p53. Cell. 2004;117:859-72 pubmed
    ..Significantly, recombinant YY1 is sufficient to induce Hdm2-mediated p53 polyubiquitination in vitro, suggesting that this function of YY1 is independent of its ..
  15. Dayal S, Sparks A, Jacob J, Allende Vega N, Lane D, Saville M. Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53. J Biol Chem. 2009;284:5030-41 pubmed publisher
    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...
  16. Boersma B, Howe T, Goodman J, Yfantis H, Lee D, Chanock S, et al. Association of breast cancer outcome with status of p53 and MDM2 SNP309. J Natl Cancer Inst. 2006;98:911-9 pubmed
    A common single-nucleotide polymorphism (SNP) in the promoter region of the MDM2 gene, known as T-309G and referred to as SNP309 for this study, leads to increased expression of Mdm2 protein and attenuated function of the p53 tumor ..
  17. Phelps M, Darley M, Primrose J, Blaydes J. p53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells. Cancer Res. 2003;63:2616-23 pubmed
    The negative-regulatory feedback loop between p53 and hdm2 forms part of a finely balanced regulatory network of proteins that controls cell cycle progression and commitment to apoptosis...
  18. Jin Y, Zeng S, Sun X, Lee H, Blattner C, Xiao Z, et al. MDMX promotes proteasomal turnover of p21 at G1 and early S phases independently of, but in cooperation with, MDM2. Mol Cell Biol. 2008;28:1218-29 pubmed
    We have shown previously that MDM2 promotes the degradation of the cyclin-dependent kinase inhibitor p21 through a ubiquitin-independent proteolytic pathway. Here we report that the MDM2 analog, MDMX, also displays a similar activity...
  19. Kass E, Poyurovsky M, Zhu Y, Prives C. Mdm2 and PCAF increase Chk2 ubiquitination and degradation independently of their intrinsic E3 ligase activities. Cell Cycle. 2009;8:430-7 pubmed
    ..1) Here we show that the S456A mutant preferentially binds to Mdm2 compared to wild-type Chk2 and downregulation of Mdm2 with siRNA can rescue the observed destabilization of S456A ..
  20. Li M, Gu W. A critical role for noncoding 5S rRNA in regulating Mdmx stability. Mol Cell. 2011;43:1023-32 pubmed publisher
    Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells...
  21. Zhang Y, Xiong Y. Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53. Mol Cell. 1999;3:579-91 pubmed
    ..the nucleolus via a sequence within the exon 2-encoded C-terminal domain and is induced to leave the nucleolus by MDM2. ARF forms nuclear bodies with MDM2 and p53 and blocks p53 and MDM2 nuclear export...
  22. Dai M, Shi D, Jin Y, Sun X, Zhang Y, Grossman S, et al. Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism. J Biol Chem. 2006;281:24304-13 pubmed
    Inhibition of the MDM2-p53 feedback loop is critical for p53 activation in response to cellular stresses...
  23. Bouska A, Lushnikova T, Plaza S, Eischen C. Mdm2 promotes genetic instability and transformation independent of p53. Mol Cell Biol. 2008;28:4862-74 pubmed publisher
    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...
  24. Cheng T, Cohen S. Human MDM2 isoforms translated differentially on constitutive versus p53-regulated transcripts have distinct functions in the p53/MDM2 and TSG101/MDM2 feedback control loops. Mol Cell Biol. 2007;27:111-9 pubmed
    Proteins encoded by the mdm2 gene, which has a pivotal role in the regulation of growth and differentiation, exist principally in human and murine cells as two isoforms that migrate in gels as 75-kDa and 90-kDa proteins...
  25. Galli F, Rossi M, D Alessandra Y, De Simone M, Lopardo T, Haupt Y, et al. MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation. J Cell Sci. 2010;123:2423-33 pubmed publisher
    ..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...
  26. Stad R, Little N, Xirodimas D, Frenk R, van der Eb A, Lane D, et al. Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms. EMBO Rep. 2001;2:1029-34 pubmed
    ..regulation of p53 activity occurs at the level of protein stability, largely determined by the activity of the Mdm2 protein...
  27. Mayo L, Seo Y, Jackson M, Smith M, Rivera Guzman J, Korgaonkar C, et al. Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J Biol Chem. 2005;280:25953-9 pubmed
    ..We found that p53 targeted MDM2 in cells in which DNA repair was occurring, but persistent DNA damage induced by chemotherapy led p53 to ..
  28. Lindström M, Jin A, Deisenroth C, White Wolf G, Zhang Y. Cancer-associated mutations in the MDM2 zinc finger domain disrupt ribosomal protein interaction and attenuate MDM2-induced p53 degradation. Mol Cell Biol. 2007;27:1056-68 pubmed
    The p53-inhibitory function of the oncoprotein MDM2 is regulated by a number of MDM2-binding proteins, including ARF and ribosomal proteins L5, L11, and L23, which bind the central acidic domain of MDM2 and inhibit its E3 ubiquitin ligase ..
  29. Ofir Rosenfeld Y, Boggs K, Michael D, Kastan M, Oren M. Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell. 2008;32:180-9 pubmed publisher
    b>Mdm2 regulates the p53 tumor suppressor by promoting its proteasome-mediated degradation. Mdm2 and p53 engage in an autoregulatory feedback loop that maintains low p53 activity in nonstressed cells...
  30. Kang S, Wang D, Li W, Wang N, Zhou R, Sun D, et al. Association of p73 and MDM2 polymorphisms with the risk of epithelial ovarian cancer in Chinese women. Int J Gynecol Cancer. 2009;19:572-7 pubmed publisher
    This study was to investigate the association of p73 G4C14-to-A4T14 and Murine Double Minute2 (MDM2) 309T/G, Del1518+/- single nucleotide polymorphisms with the risk of epithelial ovarian cancer (EOC) in Chinese...
  31. Sundqvist A, Liu G, Mirsaliotis A, Xirodimas D. Regulation of nucleolar signalling to p53 through NEDDylation of L11. EMBO Rep. 2009;10:1132-9 pubmed publisher
    ..Mouse double minute 2 (MDM2) -mediated NEDDylation protects L11 from degradation and this is required for p53 stabilization during nucleolar ..
  32. Mahata B, Sundqvist A, Xirodimas D. Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner. Oncogene. 2012;31:3060-71 pubmed publisher
    ..We found that direct binding to Mdm2 E3 ligase and NEDDylation of L11 are critical regulators for L11 promoter recruitment...
  33. Hu B, Gilkes D, Chen J. Efficient p53 activation and apoptosis by simultaneous disruption of binding to MDM2 and MDMX. Cancer Res. 2007;67:8810-7 pubmed
    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...
  34. Tang Y, Lin R, Tsai Y, Hsu H, Yang Y, Chen C, et al. MDM2 overexpression deregulates the transcriptional control of RB/E2F leading to DNA methyltransferase 3A overexpression in lung cancer. Clin Cancer Res. 2012;18:4325-33 pubmed publisher
    ..Therefore, we examined whether the transcriptional deregulation of RB/MDM2 pathway was responsible for DNMT3A overexpression and analyzed the therapeutic potential of MDM2 antagonist for ..
  35. Zhao B, Chen H, Lei N, Li G, Zhao W, Zhan Y, et al. p53 mediates the negative regulation of MDM2 by orphan receptor TR3. EMBO J. 2006;25:5703-15 pubmed
    b>MDM2 is an oncoprotein whose transforming potential is activated by overexpression. The expression level of MDM2 is negatively regulated by orphan receptor TR3 that mainly acts as a transcriptional factor to regulate gene expression...
  36. Dai M, Sun X, Lu H. Aberrant expression of nucleostemin activates p53 and induces cell cycle arrest via inhibition of MDM2. Mol Cell Biol. 2008;28:4365-76 pubmed publisher
    ..Here, we show that NS regulates p53 activity through the inhibition of MDM2. NS binds to the central acidic domain of MDM2 and inhibits MDM2-mediated p53 ubiquitylation and degradation...
  37. Hara M, Kovacs J, Whalen E, Rajagopal S, Strachan R, Grant W, et al. A stress response pathway regulates DNA damage through ?2-adrenoreceptors and ?-arrestin-1. Nature. 2011;477:349-53 pubmed publisher
    ..human cell lines, ?-arrestin-1 (ARRB1), activated via ?(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold...
  38. Shieh S, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 1997;91:325-34 pubmed
    ..15 occurs after DNA damage and that this leads to reduced interaction of p53 with its negative regulator, the oncoprotein MDM2, in vivo and in vitro...
  39. Tang J, Qu L, Pang M, Yang X. Daxx is reciprocally regulated by Mdm2 and Hausp. Biochem Biophys Res Commun. 2010;393:542-5 pubmed publisher
    ..In our previous studies, we have found that Daxx forms a complex with the E3 ubiquitin ligase Mdm2 and the de-ubiquitinase Hausp...
  40. Dong D, Gao X, Zhu Z, Yu Q, Bian S, Gao Y. A 40-bp insertion/deletion polymorphism in the constitutive promoter of MDM2 confers risk for hepatocellular carcinoma in a Chinese population. Gene. 2012;497:66-70 pubmed publisher
    ..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...
  41. Enge M, Bao W, Hedström E, Jackson S, Moumen A, Selivanova G. MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53. Cancer Cell. 2009;15:171-83 pubmed publisher
    ..We uncovered that MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription...
  42. Fang S, Jensen J, Ludwig R, Vousden K, Weissman A. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 2000;275:8945-51 pubmed
    b>Mdm2 has been shown to regulate p53 stability by targeting the p53 protein for proteasomal degradation. We now report that Mdm2 is a ubiquitin protein ligase (E3) for p53 and that its activity is dependent on its RING finger...
  43. Lu X, Ma O, Nguyen T, Jones S, Oren M, Donehower L. The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell. 2007;12:342-54 pubmed
    ..One transcriptional target of p53 is Mdm2, an E3 ubiquitin ligase that interacts with p53 to promote its proteasomal degradation in a negative feedback ..
  44. Girnita L, Shenoy S, Sehat B, Vasilcanu R, Girnita A, Lefkowitz R, et al. {beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. J Biol Chem. 2005;280:24412-9 pubmed
    ..in the regulation of G protein-coupled receptors, serves as an adaptor to bring the oncoprotein E3 ubiquitin ligase MDM2 to the IGF-1R...
  45. Grochola L, Müller T, Bond G, Taubert H, Udelnow A, Wurl P. MDM2 SNP309 associates with accelerated pancreatic adenocarcinoma formation. Pancreas. 2010;39:76-80 pubmed publisher
    The G-allele of a single nucleotide polymorphism in the promoter of the MDM2 gene (MDM2 SNP309, T/G) associates with the acceleration of tumor formation and an increased risk for developing various malignancies...
  46. Cai X, Yang M. The functional MDM2 T309G genetic variant but not P53 Arg72Pro polymorphism is associated with risk of sarcomas: a meta-analysis. J Cancer Res Clin Oncol. 2012;138:555-61 pubmed publisher
    The P53-MDM2 pathway plays a central role in sarcoma pathogenesis. Functional P53 Arg72Pro and MDM2 T309G single-nucleotide polymorphisms (SNP) are considered to have significant effects on risk of sarcomas...
  47. Grossman S, Perez M, Kung A, Joseph M, Mansur C, Xiao Z, et al. p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol Cell. 1998;2:405-15 pubmed
    ..In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer...
  48. Rizos H, Darmanian A, Mann G, Kefford R. Two arginine rich domains in the p14ARF tumour suppressor mediate nucleolar localization. Oncogene. 2000;19:2978-85 pubmed
    ..The ARF protein inhibits hdm2 activity, leading to the stabilization of the p53 tumour suppressor and cell cycle inhibition...
  49. Lahav G, Rosenfeld N, Sigal A, Geva Zatorsky N, Levine A, Elowitz M, et al. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet. 2004;36:147-50 pubmed
    ..We present a system for following, in individual living cells, the dynamics of p53 and its negative regulator Mdm2 (refs...
  50. Zhang Z, Wang H, Li M, Agrawal S, Chen X, Zhang R. MDM2 is a negative regulator of p21WAF1/CIP1, independent of p53. J Biol Chem. 2004;279:16000-6 pubmed
    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...
  51. Sato A, Sunayama J, Matsuda K, Seino S, Suzuki K, Watanabe E, et al. MEK-ERK signaling dictates DNA-repair gene MGMT expression and temozolomide resistance of stem-like glioblastoma cells via the MDM2-p53 axis. Stem Cells. 2011;29:1942-51 pubmed publisher
    ..signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK)-murine double minute 2 (MDM2)-p53 pathway plays a critical role in the regulation of MGMT expression, using stem-like glioblastoma cells ..
  52. Chaar I, Amara S, Khiari M, Ounissi D, Dhraif M, Ben Hamida A, et al. Relationship between MDM2 and p53 alterations in colorectal cancer and their involvement and prognostic value in the Tunisian population. Appl Immunohistochem Mol Morphol. 2013;21:228-36 pubmed publisher
    ..The most important regulator of this protein that was identified originally was the Murine Double Minute2 (MDM2) oncoprotein, by which the levels of p53 were fixed through an autoregulatory feedback loop...
  53. Lin H, Wang L, Hu Y, Altuwaijri S, Chang C. Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase. EMBO J. 2002;21:4037-48 pubmed
    ..Here we show that Akt and Mdm2 form a complex with AR and promote phosphorylation-dependent AR ubiquitylation, resulting in AR degradation by the ..
  54. Tang J, Qu L, Zhang J, Wang W, Michaelson J, Degenhardt Y, et al. Critical role for Daxx in regulating Mdm2. Nat Cell Biol. 2006;8:855-62 pubmed
    ..In unstressed cells, the anti-proliferative effects of p53 are restrained by mouse double minute 2 (Mdm2), a ubiquitin ligase (E3) that promotes p53 ubiquitination and degradation...
  55. Castera L, Sabbagh A, Dehainault C, Michaux D, Mansuet Lupo A, Patillon B, et al. MDM2 as a modifier gene in retinoblastoma. J Natl Cancer Inst. 2010;102:1805-8 pubmed publisher
    ..b>MDM2, which increases p53 and pRB catabolism, is therefore a prominent candidate...
  56. Herman A, Hayano M, Poyurovsky M, Shimada K, Skouta R, Prives C, et al. Discovery of Mdm2-MdmX E3 ligase inhibitors using a cell-based ubiquitination assay. Cancer Discov. 2011;1:312-25 pubmed publisher
    ..The oncogene Mdm2 is an attractive E3 ligase to target, as it is the key negative regulator of the tumor suppressor p53, which ..
  57. Unger T, Juven Gershon T, Moallem E, Berger M, Vogt Sionov R, Lozano G, et al. Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. EMBO J. 1999;18:1805-14 pubmed
    ..p53 stability and activity are negatively regulated by the murine double minute (Mdm2) oncoprotein in an autoregulatory feedback loop...
  58. Park S, Choi J, Kim E, Jang J, Han H, Lee W, et al. MDM2 309T>G polymorphism and risk of lung cancer in a Korean population. Lung Cancer. 2006;54:19-24 pubmed
    The MDM2 protein plays an important role in regulating cell proliferation and apoptosis by interaction with multiple proteins including p53 and Rb...
  59. Chen D, Zhang Z, Li M, Wang W, Li Y, Rayburn E, et al. Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 function. Oncogene. 2007;26:5029-37 pubmed
    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...
  60. Lee Y, Lim J, Chun Y, Moon H, Lee M, Huang L, et al. Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha. Carcinogenesis. 2009;30:1768-75 pubmed publisher
    ..interplay among hypoxia-inducible factor 1-alpha (HIF-1alpha), p53 and human orthologue of murine double minute 2 (Hdm2) has been introduced as a key event in tumor promotion and angiogenesis...
  61. Leveillard T, Wasylyk B. The MDM2 C-terminal region binds to TAFII250 and is required for MDM2 regulation of the cyclin A promoter. J Biol Chem. 1997;272:30651-61 pubmed
    b>MDM2 proto-oncogene expression is aberrant in many human tumors. Its normal role is to modulate the functions of p53. The N terminus of MDM2 interacts with p53, whereas the properties of the rest of the molecule are poorly understood...
  62. Carr Wilkinson J, O Toole K, Wood K, Challen C, Baker A, Board J, et al. High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma. Clin Cancer Res. 2010;16:1108-18 pubmed publisher
    ..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...
  63. Gu L, Zhang H, He J, Li J, Huang M, Zhou M. MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells. Oncogene. 2012;31:1342-53 pubmed publisher
    ..Here, we report that MYCN expression was regulated by the oncoprotein MDM2 at the post-transcriptional level and was associated with neuroblastoma cell growth...
  64. Takagi M, Absalon M, McLure K, Kastan M. Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell. 2005;123:49-63 pubmed
    ..These findings demonstrate the importance of increased translation of p53 in DNA-damage responses and suggest critical roles for RPL26 and nucleolin in affecting p53 induction. ..
  65. Salcedo A, Mayor F, Penela P. Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled receptor kinase 2. EMBO J. 2006;25:4752-62 pubmed
    ..We report that Mdm2, an E3-ubiquitin ligase involved in the control of cell growth and apoptosis, plays a key role in GRK2 degradation...
  66. Wade M, Li Y, Wahl G. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer. 2013;13:83-96 pubmed publisher
    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...
  67. Linke K, Mace P, Smith C, Vaux D, Silke J, Day C. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ. 2008;15:841-8 pubmed publisher
    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...
  68. Ellis N, Huo D, Yildiz O, Worrillow L, Banerjee M, Le Beau M, et al. MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility. Blood. 2008;112:741-9 pubmed publisher
    ..we tested associations between patients with t-AML (n = 171) and 2 common functional p53-pathway variants, the MDM2 SNP309 and the TP53 codon 72 polymorphism...
  69. Zhang Y, Liu L, Tang Y, Chen C, Wang Q, Xu J, et al. Polymorphisms in TP53 and MDM2 contribute to higher risk of colorectal cancer in Chinese population: a hospital-based, case-control study. Mol Biol Rep. 2012;39:9661-8 pubmed publisher
    The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis...