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. Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, et al. Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nat Med. 2011;17:944-51 pubmed publisher
    ..Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1...
  4. 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...
  5. 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
    ..Targeting the E3 ubiquitin ligase HDM2 can lead to a therapeutic surge in p53 levels...
  6. 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
    ..factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice)...
  7. 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...
  8. 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...
  9. 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...

More Information

Publications317 found, 100 shown here

  1. 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...
  2. 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)...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef L, Masucci M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med. 2004;10:1321-8 pubmed
    ..RITA may serve as a lead compound for the development of an anticancer drug that targets tumors with wild-type p53. ..
  14. Sun X, Dai M, Lu H. 5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction. J Biol Chem. 2007;282:8052-9 pubmed
    ..Here we report that 5-FU treatment leads to p53 stabilization and activation by blocking MDM2 feedback inhibition through ribosomal proteins...
  15. Chua H, Ng D, Choo S, Lum S, Li H, Soh L, et al. Effect of MDM2 SNP309 and p53 codon 72 polymorphisms on lung cancer risk and survival among non-smoking Chinese women in Singapore. BMC Cancer. 2010;10:88 pubmed publisher
    Single nucleotide polymorphism (SNP) 309 resulting in a T or G allele in the promoter of MDM2, the negative regulator of p53, has been suggested to affect cancer predisposition and age of onset, primarily in females...
  16. Kussie P, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine A, et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science. 1996;274:948-53 pubmed
    The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription...
  17. Liu J, Zhang X, Guo Y, Sun T, Lin D, Wen T. [Genetic polymorphism in MDM2 is associated with susceptibility to colorectal cancer in a Chinese population]. Zhonghua Zhong Liu Za Zhi. 2008;30:335-8 pubmed
    ..Mouse double minute 2 (MDM2) gene is a key negative regulator of p53 pathway and overexpressed in many cancers as oncoprotein...
  18. Goldberg Z, Vogt Sionov R, Berger M, Zwang Y, Perets R, Van Etten R, et al. Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation. EMBO J. 2002;21:3715-27 pubmed
    The p53 tumor suppressor is inhibited and destabilized by Mdm2. However, under stress conditions, this downregulation is relieved, allowing the accumulation of biologically active p53...
  19. Girnita L, Girnita A, Larsson O. Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor. Proc Natl Acad Sci U S A. 2003;100:8247-52 pubmed
    ..This effect, which was independent of the p53 status (i.e., wild type or mutated), was prevented if Mdm2 was coinhibited...
  20. Jin Y, Lee H, Zeng S, Dai M, Lu H. MDM2 promotes p21waf1/cip1 proteasomal turnover independently of ubiquitylation. EMBO J. 2003;22:6365-77 pubmed
    The CDK inhibitor p21waf1/cip1 is degraded by a ubiquitin-independent proteolytic pathway. Here, we show that MDM2 mediates this degradation process...
  21. Meng L, Lin T, Tsai R. Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M progression and cell survival. J Cell Sci. 2008;121:4037-46 pubmed publisher
    Nucleolar disassembly occurs during mitosis and nucleolar stress, releasing several MDM2-interactive proteins residing in the nucleolus that share the common activity of p53 stabilization...
  22. Nunobiki O, Ueda M, Yamamoto M, Toji E, Sato N, Izuma S, et al. Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer. Hum Cell. 2009;22:101-6 pubmed publisher
    Genetic polymorphisms of p53 and its negative regulator murine double minute 2 homolog (MDM2) have been shown to be closely associated with tumorigenesis in a variety of human cancers...
  23. Stott F, Bates S, James M, McConnell B, Starborg M, Brookes S, et al. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2. EMBO J. 1998;17:5001-14 pubmed
    ..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. Millikan R, Heard K, Winkel S, Hill E, Heard K, Massa B, et al. No association between the MDM2 -309 T/G promoter polymorphism and breast cancer in African-Americans or Whites. Cancer Epidemiol Biomarkers Prev. 2006;15:175-7 pubmed
  25. Kojima K, Shimanuki M, Shikami M, Samudio I, Ruvolo V, Corn P, et al. The dual PI3 kinase/mTOR inhibitor PI-103 prevents p53 induction by Mdm2 inhibition but enhances p53-mediated mitochondrial apoptosis in p53 wild-type AML. Leukemia. 2008;22:1728-36 pubmed publisher
    ..of the rapamycin (PI3K/Akt/mTOR) pathway and inactivation of wild-type p53 by murine double minute 2 homologue (Mdm2) overexpression are frequent molecular events in acute myeloid leukemia (AML)...
  26. Han J, Lee G, Jang D, Lee S, Lee J. Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancer. Cancer. 2008;113:799-807 pubmed publisher
    The purpose of the study was to investigate whether polymorphisms of p53 codon 72 (Arg72Pro) and MDM2 SNP309 (309T>G) affect p53 expression and the clinical outcome of patients with advanced nonsmall cell lung cancer (NSCLC)...
  27. Poyurovsky M, Katz C, Laptenko O, Beckerman R, Lokshin M, Ahn J, et al. The C terminus of p53 binds the N-terminal domain of MDM2. Nat Struct Mol Biol. 2010;17:982-9 pubmed publisher
    The p53 tumor suppressor interacts with its negative regulator Mdm2 via the former's N-terminal region and core domain, yet the extreme p53 C-terminal region contains lysine residues ubiquitinated by Mdm2 and can bear post-translational ..
  28. Thut C, Goodrich J, Tjian R. Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev. 1997;11:1974-86 pubmed
    The oncoprotein MDM2 binds to the activation domain of the tumor suppressor p53 and inhibits its ability to stimulate transcription...
  29. Zhang Y, Xiong Y, Yarbrough W. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell. 1998;92:725-34 pubmed
    ..We show here that ARF binds to MDM2 and promotes the rapid degradation of MDM2...
  30. Honda R, Yasuda H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene. 2000;19:1473-6 pubmed
    We previously showed that oncoprotein MDM2 has ubiquitin ligase activity toward tumor suppressor p53. In that paper, we showed very weak homology in the carboxyl terminal portion between MDM2 and E6AP (HECT domain)...
  31. Okamoto K, Li H, Jensen M, Zhang T, Taya Y, Thorgeirsson S, et al. Cyclin G recruits PP2A to dephosphorylate Mdm2. Mol Cell. 2002;9:761-71 pubmed
    ..Interestingly, cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216...
  32. Xiong L, Kou F, Yang Y, Wu J. A novel role for IGF-1R in p53-mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop. J Cell Biol. 2007;178:995-1007 pubmed
    ..We show that inhibition or loss of IGF-1R activity reduces translational synthesis of p53 and Mdm2 protein...
  33. Xu H, Zhang Z, Li M, Zhang R. MDM2 promotes proteasomal degradation of p21Waf1 via a conformation change. J Biol Chem. 2010;285:18407-14 pubmed publisher
    b>MDM2 plays a major role in cancer development and progression via both p53-dependent and -independent functions. One of its p53-independent functions is the induction of the ubiquitin-independent proteasomal degradation of p21(Waf1)...
  34. Phillips A, Teunisse A, Lam S, Lodder K, Darley M, Emaduddin M, et al. HDMX-L is expressed from a functional p53-responsive promoter in the first intron of the HDMX gene and participates in an autoregulatory feedback loop to control p53 activity. J Biol Chem. 2010;285:29111-27 pubmed publisher
    ..at low levels and is largely inactive, mainly through the action of its two essential negative regulators, HDM2 and HDMX. p53 abundance and activity are up-regulated in response to various stresses, including DNA damage and oncogene ..
  35. Dong H, Fang C, Fan L, Zhu D, Wang D, Zhu H, et al. MDM2 promoter SNP309 is associated with an increased susceptibility to chronic lymphocytic leukemia and correlates with MDM2 mRNA expression in Chinese patients with CLL. Int J Cancer. 2012;130:2054-61 pubmed publisher
    A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has recently been suggested as an unfavorable prognostic marker in chronic ..
  36. Amson R, Pece S, Lespagnol A, Vyas R, Mazzarol G, Tosoni D, et al. Reciprocal repression between P53 and TCTP. Nat Med. 2011;18:91-9 pubmed publisher
    ..TCTP promotes P53 degradation by competing with NUMB for binding to P53-MDM2-containing complexes...
  37. Xiao Z, Chen J, Levine A, Modjtahedi N, Xing J, Sellers W, et al. Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature. 1995;375:694-8 pubmed
    ..The cellular oncoprotein, Mdm2, binds to and downmodulates p53 function; its human homologue, MDM2, is amplified in certain human tumours, ..
  38. Landers J, Cassel S, George D. Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein. Cancer Res. 1997;57:3562-8 pubmed
    The mdm2 oncogene has transforming potential that is activated by overexpression...
  39. Deb S. Function and dysfunction of the human oncoprotein MDM2. Front Biosci. 2002;7:d235-43 pubmed
    The protein MDM2 coded by the human homologue of mouse double minute-2 (mdm2) gene frequently overexpresses in malignant human breast and other tumors...
  40. Heron Milhavet L, LeRoith D. Insulin-like growth factor I induces MDM2-dependent degradation of p53 via the p38 MAPK pathway in response to DNA damage. J Biol Chem. 2002;277:15600-6 pubmed
    ..Degradation of the p53 protein was associated with an increase in MDM2, an upstream modulator of the half-life and activity of the p53 protein...
  41. Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, et al. Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem. 2002;277:21843-50 pubmed
    ..b>Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good ..
  42. Pereg Y, Shkedy D, de Graaf P, Meulmeester E, Edelson Averbukh M, Salek M, et al. Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage. Proc Natl Acad Sci U S A. 2005;102:5056-61 pubmed
    ..Here we show that efficient damage-induced degradation of human Hdmx depends on functional ATM and at least three sites on the Hdmx that are phosphorylated in response to DSBs...
  43. Xia M, Knezevic D, Tovar C, Huang B, Heimbrook D, Vassilev L. Elevated MDM2 boosts the apoptotic activity of p53-MDM2 binding inhibitors by facilitating MDMX degradation. Cell Cycle. 2008;7:1604-12 pubmed
    ..Many tumors overproduce its negative regulator MDM2, a specific p53 ubiquitin ligase and transcriptional inhibitor, to disable p53 function...
  44. Li B, Cheng Q, Li Z, Chen J. p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumors. Cell Cycle. 2010;9:1411-20 pubmed
    ..Here we show that disruption of p53-MDM2 binding using the MDM2-specific inhibitor Nutlin activates p53 in TGCT cells and is sufficient to induce strong ..
  45. Di Stefano V, Mattiussi M, Sacchi A, D Orazi G. HIPK2 inhibits both MDM2 gene and protein by, respectively, p53-dependent and independent regulations. FEBS Lett. 2005;579:5473-80 pubmed
    We address here the involvement of the homeodomain-interacting protein kinase 2 (HIPK2)/p53 complex on MDM2 regulation following apoptotic DNA damage...
  46. Coutts A, Adams C, La Thangue N. p53 ubiquitination by Mdm2: a never ending tail?. DNA Repair (Amst). 2009;8:483-90 pubmed publisher
    ..b>Mdm2 mediates ubiquitin-dependent degradation of p53 which plays a key role in maintaining cellular p53 levels...
  47. Liu J, Chung H, Vogt M, Jin Y, Malide D, He L, et al. JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. EMBO J. 2011;30:846-58 pubmed publisher
    ..The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress. ..
  48. Chene P, Fuchs J, Carena I, Furet P, Garcia Echeverria C. Study of the cytotoxic effect of a peptidic inhibitor of the p53-hdm2 interaction in tumor cells. FEBS Lett. 2002;529:293-7 pubmed
    Inhibitors of the p53-hdm2 interaction are attractive molecules for stimulating the p53 pathway in tumors...
  49. Dai M, Lu H. Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5. J Biol Chem. 2004;279:44475-82 pubmed
    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...
  50. Zhang X, Miao X, Guo Y, Tan W, Zhou Y, Sun T, et al. Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer. Hum Mutat. 2006;27:110-7 pubmed
    ..b>MDM2 is a key negative regulator of the TP53 pathway and is overexpressed in many cancers as oncoprotein...
  51. El Hallani S, Marie Y, Idbaih A, Rodero M, Boisselier B, Laigle Donadey F, et al. No association of MDM2 SNP309 with risk of glioblastoma and prognosis. J Neurooncol. 2007;85:241-4 pubmed
    The MDM2 SNP309 variant has been shown to increase MDM2 expression and to be associated with tumor formation. In glioblastomas, the P53/MDM2 pathway is of crucial importance and MDM2 amplification is related to poor prognosis...
  52. Hirata H, Hinoda Y, Kikuno N, Kawamoto K, Suehiro Y, Tanaka Y, et al. MDM2 SNP309 polymorphism as risk factor for susceptibility and poor prognosis in renal cell carcinoma. Clin Cancer Res. 2007;13:4123-9 pubmed
    b>MDM2 is a major negative regulator of p53, and a single nucleotide polymorphism in the MDM2 promoter region SNP309 (rs2279744) has been shown to increase the affinity of the transcriptional activator Sp1, resulting in elevated MDM2 ..
  53. Ueda M, Yamamoto M, Nunobiki O, Toji E, Sato N, Izuma S, et al. Murine double-minute 2 homolog single nucleotide polymorphism 309 and the risk of gynecologic cancer. Hum Cell. 2009;22:49-54 pubmed publisher
    ..germline polymorphism in the promoter region of murine double-minute 2 homolog single nucleotide polymorphism 309 (MDM2-SNP309) has been reported to profoundly accelerate tumor formation, suggesting that it may also represent a ..
  54. Zhang Y, Wang J, Yuan Y, Zhang W, Guan W, Wu Z, et al. Negative regulation of HDM2 to attenuate p53 degradation by ribosomal protein L26. Nucleic Acids Res. 2010;38:6544-54 pubmed publisher
    b>HDM2 is a p53-specific E3 ubiquitin ligase. Its overexpression leads to excessive inactivation of tumor protein p53, diminishing its tumor suppressor function...
  55. Zhou S, Gu L, He J, Zhang H, Zhou M. MDM2 regulates vascular endothelial growth factor mRNA stabilization in hypoxia. Mol Cell Biol. 2011;31:4928-37 pubmed publisher
    ..Herein, we report that the MDM2 oncoprotein plays a role in hypoxia-mediated VEGF upregulation...
  56. Zhou X, Hao Q, Liao J, Zhang Q, Lu H. Ribosomal protein S14 unties the MDM2-p53 loop upon ribosomal stress. Oncogene. 2013;32:388-96 pubmed publisher
    The MDM2-p53 feedback loop is crucially important for restricting p53 level and activity during normal cell growth and proliferation, and is thus subjected to dynamic regulation in order for cells to activate p53 upon various stress ..
  57. Gu J, Kawai H, Nie L, Kitao H, Wiederschain D, Jochemsen A, et al. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J Biol Chem. 2002;277:19251-4 pubmed
    MDMX, an MDM2-related protein, has emerged as yet another essential negative regulator of p53 tumor suppressor, since loss of MDMX expression results in p53-dependent embryonic lethality in mice...
  58. Volk E, Schuster K, Nemeth K, Fan L, Harris L. MDM2-A, a common Mdm2 splice variant, causes perinatal lethality, reduced longevity and enhanced senescence. Dis Model Mech. 2009;2:47-55 pubmed publisher
    b>MDM2 is the predominant negative regulator of p53 that functions to maintain the appropriate level of expression and activity of this central tumor suppressor...
  59. Izumi T, Io K, Matsui M, Shirakawa K, Shinohara M, Nagai Y, et al. HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replication. Proc Natl Acad Sci U S A. 2010;107:20798-803 pubmed publisher
    ..Vif enhances the stability and transcriptional activity of TP53 by blocking the MDM2-mediated ubiquitination and nuclear export of TP53...
  60. Swinney R, Hsu S, Hirschman B, Chen T, Tomlinson G. MDM2 promoter variation and age of diagnosis of acute lymphoblastic leukemia. Leukemia. 2005;19:1996-8 pubmed
  61. Zhu Y, Poyurovsky M, Li Y, Biderman L, Stahl J, Jacq X, et al. Ribosomal protein S7 is both a regulator and a substrate of MDM2. Mol Cell. 2009;35:316-26 pubmed publisher
    b>MDM2 associates with ribosomal protein S7, and this interaction is required to inhibit MDM2's E3 ligase activity, leading to stabilization of MDM2 and p53...
  62. Cross B, Chen L, Cheng Q, Li B, Yuan Z, Chen J. Inhibition of p53 DNA binding function by the MDM2 protein acidic domain. J Biol Chem. 2011;286:16018-29 pubmed publisher
    b>MDM2 regulates p53 predominantly by promoting p53 ubiquitination. However, ubiquitination-independent mechanisms of MDM2 have also been implicated. Here we show that MDM2 inhibits p53 DNA binding activity in vitro and in vivo...
  63. Haupt Y, Maya R, Kazaz A, Oren M. Mdm2 promotes the rapid degradation of p53. Nature. 1997;387:296-9 pubmed
    ..The Mdm2 oncoprotein is a potent inhibitor of p53...
  64. Mayo L, Donner D. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci U S A. 2001;98:11598-603 pubmed
    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...
  65. Millon R, Muller D, Schultz I, Salvi R, Ghnassia J, Frebourg T, et al. Loss of MDM2 expression in human head and neck squamous cell carcinomas and clinical significance. Oral Oncol. 2001;37:620-31 pubmed
    The transforming potential of the MDM2 oncogene has been attributed to the overproduction of the protein...
  66. Okumura N, Saji S, Eguchi H, Nakashima S, Saji S, Hayashi S. Distinct promoter usage of mdm2 gene in human breast cancer. Oncol Rep. 2002;9:557-63 pubmed
    Human breast cancers, especially estrogen receptor alpha (ER(alpha))-positive ones, often overexpress the oncoprotein MDM2 without mdm2 gene amplification...
  67. Yang Z, Wang L. An autoregulatory feedback loop between Mdm2 and SHP that fine tunes Mdm2 and SHP stability. FEBS Lett. 2012;586:1135-40 pubmed publisher
    b>Mdm2 is a crucial negative regulator of the tumor suppressor function of p53. However, little is known about Mdm2 protein stability regulation by other tumor suppressors...
  68. Bursac S, Brdovcak M, Pfannkuchen M, Orsolic I, Golomb L, Zhu Y, et al. Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress. Proc Natl Acad Sci U S A. 2012;109:20467-72 pubmed publisher
    ..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 ..
  69. Gu L, Zhu N, Zhang H, Durden D, Feng Y, Zhou M. Regulation of XIAP translation and induction by MDM2 following irradiation. Cancer Cell. 2009;15:363-75 pubmed publisher
    ..Herein we demonstrate that the upregulation of XIAP protein levels is regulated by MDM2 at the translational level...
  70. Gajjar M, Candeias M, Malbert Colas L, Mazars A, Fujita J, Olivares Illana V, et al. The p53 mRNA-Mdm2 interaction controls Mdm2 nuclear trafficking and is required for p53 activation following DNA damage. Cancer Cell. 2012;21:25-35 pubmed publisher
    ..The ATM substrate Mdm2 controls p53 activity by either targeting p53 for degradation or promoting its synthesis by binding the p53 mRNA...
  71. Bernardi R, Scaglioni P, Bergmann S, Horn H, Vousden K, Pandolfi P. PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol. 2004;6:665-72 pubmed
    ..PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); however, the mechanism by which PML regulates Mdm2 remains unclear...
  72. Nakashima M, Kondo S, Shimizu Y, Wakisaka N, Murono S, Furukawa M, et al. Impact of MDM2 single nucleotide polymorphism on tumor onset in head and neck squamous cell carcinoma. Acta Otolaryngol. 2008;128:808-13 pubmed publisher
    The GG genotype of MDM2 SNP309 is associated with an earlier onset of head and neck squamous cell carcinoma (HNSCC) in the Japanese population...
  73. Cheng Q, Chen J. The phenotype of MDM2 auto-degradation after DNA damage is due to epitope masking by phosphorylation. Cell Cycle. 2011;10:1162-6 pubmed
    It is widely accepted that DNA damage induces rapid degradation of MDM2 through phosphorylation, resulting in a transient reduction of MDM2 level. Elimination of MDM2 is a logical mechanism that stabilizes p53...
  74. Coffill C, Muller P, Oh H, Neo S, Hogue K, Cheok C, et al. Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion. EMBO Rep. 2012;13:638-44 pubmed publisher
    ..Advanced proteomics has thus allowed the detection of a new mechanism of p53-driven invasion. ..
  75. Ma H, Huang T, Han F, Chen W. Association between MDM2 promoter SNP309 T/G polymorphism and liver cancer risk - a meta-analysis. Asian Pac J Cancer Prev. 2012;13:2841-6 pubmed
    Many studies have investigated the association between the MDM2 promoter SNP309 T/G polymorphism and liver cancer risk, but inconsistencies make drawwing definitive conclusions difficult...
  76. Sdek P, Ying H, Zheng H, Margulis A, Tang X, Tian K, et al. The central acidic domain of MDM2 is critical in inhibition of retinoblastoma-mediated suppression of E2F and cell growth. J Biol Chem. 2004;279:53317-22 pubmed
    ..Inactivation of Rb plays a critical role in the development of human malignancies. MDM2, an oncogene frequently found amplified and overexpressed in a variety of human tumors and cancers, directly ..
  77. Wilkening S, Hemminki K, Rudnai P, Gurzau E, Koppova K, Forsti A, et al. No association between MDM2 SNP309 promoter polymorphism and basal cell carcinoma of the skin. Br J Dermatol. 2007;157:375-7 pubmed
    The MDM2 oncoprotein promotes cell survival and cell cycle progression by inhibiting the p53 tumour suppressor protein. Further, overexpression of the MDM2 gene can inhibit DNA double-strand break repair in a p53-independent manner...
  78. Bartel F, Taylor A, Taubert H, Harris L. Novel mdm2 splice variants identified in pediatric rhabdomyosarcoma tumors and cell lines. Oncol Res. 2001;12:451-7 pubmed
    b>Mdm2 is an oncogene that binds to and inactivates the tumor suppressor p53...
  79. Horn H, Vousden K. Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway. Oncogene. 2008;27:5774-84 pubmed publisher
    b>MDM2 is a ubiquitin ligase that plays a key role in regulating the stability of the p53 tumor suppressor protein...
  80. Markey M, Berberich S. Full-length hdmX transcripts decrease following genotoxic stress. Oncogene. 2008;27:6657-66 pubmed publisher
    ..transcribed, and that MdmX protein activity is instead controlled by cellular localization and DNA damage induced Mdm2-mediated ubiquitination leading to proteasomal degradation...
  81. Wang X, Arooz T, Siu W, Chiu C, Lau A, Yamashita K, et al. MDM2 and MDMX can interact differently with ARF and members of the p53 family. FEBS Lett. 2001;490:202-8 pubmed
    Members of the p53 family of transcription factors have essential roles in tumor suppression and in development. MDM2 is an essential regulator of p53 that can inhibit the transcriptional activity of p53, shuttle p53 out of the nucleus, ..
  82. Busso C, Iwakuma T, Izumi T. Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway. Oncogene. 2009;28:1616-25 pubmed publisher
    ..occurred specifically at Lys residues near the N-terminus, and was markedly enhanced by mouse double minute 2 (MDM2), the major intracellular p53 inhibitor...
  83. Okamoto K, Taya Y, Nakagama H. Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase. FEBS Lett. 2009;583:2710-4 pubmed publisher
    b>mdm2 and mdmx oncogenes play essential yet non-redundant roles in synergistic inactivation of the tumor suppressor, p53...
  84. Kobet E, Zeng X, Zhu Y, Keller D, Lu H. MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins. Proc Natl Acad Sci U S A. 2000;97:12547-52 pubmed
    p300 acetylates and activates the tumor suppressor p53 after DNA damage. Here, we show that MDM2, a negative-feedback regulator of p53, inhibited p300-mediated p53 acetylation by complexing with these two proteins...
  85. Dai M, Zeng S, Jin Y, Sun X, David L, Lu H. Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition. Mol Cell Biol. 2004;24:7654-68 pubmed
    The p53-MDM2 feedback loop is vital for cell growth control and is subjected to multiple regulations in response to various stress signals. Here we report another regulator of this loop...
  86. Sasaki M, Nie L, Maki C. MDM2 binding induces a conformational change in p53 that is opposed by heat-shock protein 90 and precedes p53 proteasomal degradation. J Biol Chem. 2007;282:14626-34 pubmed
    ..degradation was blocked during recovery from stress treatment and in cells co-expressing p53 and MDM2. This suggests that conformational change precedes wild-type p53 degradation by the proteasome...
  87. De Nicola F, Bruno T, Iezzi S, Di Padova M, Floridi A, Passananti C, et al. The prolyl isomerase Pin1 affects Che-1 stability in response to apoptotic DNA damage. J Biol Chem. 2007;282:19685-91 pubmed
    ..with the peptidyl-prolyl isomerase Pin1 and that conformational changes generated by Pin1 are required for Che-1/HDM2 interaction...