Autoactivation of the MDM2 E3 Ligase by Intramolecular Interaction

REFERENCES

• Vousden KH, Lane DP. 2007. p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8:275–283. http://dx.doi.org/10.1038/nrm2147.
   PubMed Web of Science ®Google Scholar
• Kubbutat MH, Jones SN, Vousden KH. 1997. Regulation of p53 stability by Mdm2. Nature 387:299–303. http://dx.doi.org/10.1038/387299a0.
   PubMed Web of Science ®Google Scholar
• Haupt Y, Maya R, Kazaz A, Oren M. 1997. Mdm2 promotes the rapid degradation of p53. Nature 387:296–299. http://dx.doi.org/10.1038/387296a0.
   PubMed Web of Science ®Google Scholar
• Montes de Oca Luna R, Wagner DS, Lozano G. 1995. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378:203–206. http://dx.doi.org/10.1038/378203a0.
   PubMed Web of Science ®Google Scholar
• Grier JD, Xiong S, Elizondo-Fraire AC, Parant JM, Lozano G. 2006. Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4. Mol. Cell. Biol. 26:192–198. http://dx.doi.org/10.1128/MCB.26.1.192-198.2006.
   PubMed Web of Science ®Google Scholar
• Jones SN, Roe AE, Donehower LA, Bradley A. 1995. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378:206–208. http://dx.doi.org/10.1038/378206a0.
   PubMed Web of Science ®Google Scholar
• Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. 2004. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303:844–848. http://dx.doi.org/10.1126/science.1092472.
   PubMed Web of Science ®Google Scholar
• Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, Nikolovska-Coleska Z, Ding K, Wang G, Chen J, Bernard D, Zhang J, Lu Y, Gu Q, Shah RB, Pienta KJ, Ling X, Kang S, Guo M, Sun Y, Yang D, Wang S. 2008. Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc. Natl. Acad. Sci. U. S. A. 105:3933–3938. http://dx.doi.org/10.1073/pnas.0708917105.
   PubMed Web of Science ®Google Scholar
• Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, Heil F, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT, Nichols GL, Bui BN. 2012. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Lancet Oncol. 13:1133–1140. http://dx.doi.org/10.1016/S1470-2045(12)70474-6.
   PubMed Web of Science ®Google Scholar
• Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM. 2000. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem. 275:8945–8951. http://dx.doi.org/10.1074/jbc.275.12.8945.
   PubMed Web of Science ®Google Scholar
• Honda R, Tanaka H, Yasuda H. 1997. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420:25–27. http://dx.doi.org/10.1016/S0014-5793(97)01480-4.
   PubMed Web of Science ®Google Scholar
• Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, Woods YL, Lane DP. 2004. Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J. Biol. Chem. 279:42169–42181. http://dx.doi.org/10.1074/jbc.M403362200.
   PubMedGoogle Scholar
• Shieh SY, Ikeda M, Taya Y, Prives C. 1997. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91:325–334. http://dx.doi.org/10.1016/S0092-8674(00)80416-X.
   PubMed Web of Science ®Google Scholar
• Chao C, Herr D, Chun J, Xu Y. 2006. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J. 25:2615–2622. http://dx.doi.org/10.1038/sj.emboj.7601167.
   PubMed Web of Science ®Google Scholar
• Cheng Q, Chen L, Li Z, Lane WS, Chen J. 2009. ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. EMBO J. 28:3857–3867. http://dx.doi.org/10.1038/emboj.2009.294.
   PubMed Web of Science ®Google Scholar
• Cheng Q, Cross B, Li B, Chen L, Li Z, Chen J. 2011. Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage. Mol. Cell. Biol. 31:4951–4963. http://dx.doi.org/10.1128/MCB.05553-11.
   PubMed Web of Science ®Google Scholar
• Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M. 2001. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev. 15:1067–1077. http://dx.doi.org/10.1101/gad.886901.
   PubMed Web of Science ®Google Scholar
• Sherr CJ. 2006. Divorcing ARF and p53: an unsettled case. Nat. Rev. Cancer 6:663–673. http://dx.doi.org/10.1038/nrc1954.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, Burkhart WA, Xiong Y. 2003. Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol. Cell. Biol. 23:8902–8912. http://dx.doi.org/10.1128/MCB.23.23.8902-8912.2003.
   PubMed Web of Science ®Google Scholar
• Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH. 2003. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3:577–587. http://dx.doi.org/10.1016/S1535-6108(03)00134-X.
   PubMed Web of Science ®Google Scholar
• Deshaies RJ, Joazeiro CA. 2009. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78:399–434. http://dx.doi.org/10.1146/annurev.biochem.78.101807.093809.
   PubMed Web of Science ®Google Scholar
• Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA. 2008. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134:995–1006. http://dx.doi.org/10.1016/j.cell.2008.07.022.
   PubMed Web of Science ®Google Scholar
• Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP. 2002. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416:703–709. http://dx.doi.org/10.1038/416703a.
   PubMed Web of Science ®Google Scholar
• Plechanovova A, Jaffray EG, Tatham MH, Naismith JH, Hay RT. 2012. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature 489:115–120. http://dx.doi.org/10.1038/nature11376.
   PubMedGoogle Scholar
• Kawai H, Wiederschain D, Yuan ZM. 2003. Critical contribution of the MDM2 acidic domain to p53 ubiquitination. Mol. Cell. Biol. 23:4939–4947. http://dx.doi.org/10.1128/MCB.23.14.4939-4947.2003.
   PubMed Web of Science ®Google Scholar
• Meulmeester E, Frenk R, Stad R, de Graaf P, Marine JC, Vousden KH, Jochemsen AG. 2003. Critical role for a central part of Mdm2 in the ubiquitylation of p53. Mol. Cell. Biol. 23:4929–4938. http://dx.doi.org/10.1128/MCB.23.14.4929-4938.2003.
   PubMed Web of Science ®Google Scholar
• Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher FJIII, Chen J. 2005. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO J. 24:3279–3290. http://dx.doi.org/10.1038/sj.emboj.7600791.
   PubMed Web of Science ®Google Scholar
• Sui G, Affar EB, Shi Y, Brignone C, Wall NR, Yin P, Donohoe M, Luke MP, Calvo D, Grossman SR, Shi Y. 2004. Yin Yang 1 is a negative regulator of p53. Cell 117:859–872. http://dx.doi.org/10.1016/j.cell.2004.06.004.
   PubMed Web of Science ®Google Scholar
• Chen L, Li Z, Zwolinska AK, Smith MA, Cross B, Koomen J, Yuan ZM, Jenuwein T, Marine JC, Wright KL, Chen J. 2010. MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. EMBO J. 29:2538–2552. http://dx.doi.org/10.1038/emboj.2010.140.
   PubMed Web of Science ®Google Scholar
• Hu M, Gu L, Li M, Jeffrey PD, Gu W, Shi Y. 2006. Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway. PLoS Biol. 4:e27. http://dx.doi.org/10.1371/journal.pbio.0040027.
   PubMedGoogle Scholar
• Midgley CA, Desterro JM, Saville MK, Howard S, Sparks A, Hay RT, Lane DP. 2000. An N-terminal p14ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo. Oncogene 19:2312–2323. http://dx.doi.org/10.1038/sj.onc.1203593.
   PubMed Web of Science ®Google Scholar
• Ma J, Martin JD, Zhang H, Auger KR, Ho TF, Kirkpatrick RB, Grooms MH, Johanson KO, Tummino PJ, Copeland RA, Lai Z. 2006. A second p53 binding site in the central domain of Mdm2 is essential for p53 ubiquitination. Biochemistry 45:9238–9245. http://dx.doi.org/10.1021/bi060661u.
   PubMed Web of Science ®Google Scholar
• Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, Fersht AR. 2006. The central region of HDM2 provides a second binding site for p53. Proc. Natl. Acad. Sci. U. S. A. 103:1227–1232. http://dx.doi.org/10.1073/pnas.0510343103.
   PubMed Web of Science ®Google Scholar
• Burch LR, Midgley CA, Currie RA, Lane DP, Hupp TR. 2000. Mdm2 binding to a conformationally sensitive domain on p53 can be modulated by RNA. FEBS Lett. 472:93–98. http://dx.doi.org/10.1016/S0014-5793(00)01427-7.
   PubMed Web of Science ®Google Scholar
• Cross B, Chen L, Cheng Q, Li B, Yuan ZM, Chen J. 2011. Inhibition of p53 DNA binding function by the MDM2 protein acidic domain. J. Biol. Chem. 286:16018–16029. http://dx.doi.org/10.1074/jbc.M111.228981.
   PubMed Web of Science ®Google Scholar
• Sasaki M, Nie L, Maki CG. 2007. MDM2 binding induces a conformational change in p53 that is opposed by heat-shock protein 90 and precedes p53 proteasomal degradation. J. Biol. Chem. 282:14626–14634. http://dx.doi.org/10.1074/jbc.M610514200.
   PubMed Web of Science ®Google Scholar
• Dunker AK, Silman I, Uversky VN, Sussman JL. 2008. Function and structure of inherently disordered proteins. Curr. Opin. Struct. Biol. 18:756–764. http://dx.doi.org/10.1016/j.sbi.2008.10.002.
   PubMed Web of Science ®Google Scholar
• Dyson HJ, Wright PE. 2005. Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6:197–208. http://dx.doi.org/10.1038/nrm1589.
   PubMed Web of Science ®Google Scholar
• Blattner C, Hay T, Meek DW, Lane DP. 2002. Hypophosphorylation of Mdm2 augments p53 stability. Mol. Cell. Biol. 22:6170–6182. http://dx.doi.org/10.1128/MCB.22.17.6170-6182.2002.
   PubMed Web of Science ®Google Scholar
• Winter M, Milne D, Dias S, Kulikov R, Knippschild U, Blattner C, Meek D. 2004. Protein kinase CK1delta phosphorylates key sites in the acidic domain of murine double-minute clone 2 protein (MDM2) that regulate p53 turnover. Biochemistry 43:16356–16364. http://dx.doi.org/10.1021/bi0489255.
   PubMed Web of Science ®Google Scholar
• Kulikov R, Boehme KA, Blattner C. 2005. Glycogen synthase kinase 3-dependent phosphorylation of Mdm2 regulates p53 abundance. Mol. Cell. Biol. 25:7170–7180. http://dx.doi.org/10.1128/MCB.25.16.7170-7180.2005.
   PubMedGoogle Scholar
• Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, Wan L, Ang XL, Mock C, Yin H, Stommel JM, Gygi S, Lahav G, Asara J, Xiao ZX, Kaelin WGJr, Harper JW, Wei W. 2010. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell 18:147–159. http://dx.doi.org/10.1016/j.ccr.2010.06.015.
   PubMed Web of Science ®Google Scholar
• Kulikov R, Letienne J, Kaur M, Grossman SR, Arts J, Blattner C. 2010. Mdm2 facilitates the association of p53 with the proteasome. Proc. Natl. Acad. Sci. U. S. A. 107:10038–10043. http://dx.doi.org/10.1073/pnas.0911716107.
   PubMed Web of Science ®Google Scholar
• Chen J, Marechal V, Levine AJ. 1993. Mapping of the p53 and mdm-2 interaction domains. Mol. Cell. Biol. 13:4107–4114.
   PubMed Web of Science ®Google Scholar
• Plechanovova A, Jaffray EG, McMahon SA, Johnson KA, Navratilova I, Naismith JH, Hay RT. 2011. Mechanism of ubiquitylation by dimeric RING ligase RNF4. Nat. Struct. Mol. Biol. 18:1052–1059. http://dx.doi.org/10.1038/nsmb.2108.
   PubMedGoogle Scholar
• Bothner B, Lewis WS, DiGiammarino EL, Weber JD, Bothner SJ, Kriwacki RW. 2001. Defining the molecular basis of Arf and Hdm2 interactions. J. Mol. Biol. 314:263–277. http://dx.doi.org/10.1006/jmbi.2001.5110.
   PubMedGoogle Scholar
• Chen L, Marechal V, Moreau J, Levine AJ, Chen J. 1997. Proteolytic cleavage of the mdm2 oncoprotein during apoptosis. J. Biol. Chem. 272:22966–22973. http://dx.doi.org/10.1074/jbc.272.36.22966.
   PubMed Web of Science ®Google Scholar
• Sivakolundu SG, Nourse A, Moshiach S, Bothner B, Ashley C, Satumba J, Lahti J, Kriwacki RW. 2008. Intrinsically unstructured domains of Arf and Hdm2 form bimolecular oligomeric structures in vitro and in vivo. J. Mol. Biol. 384:240–254. http://dx.doi.org/10.1016/j.jmb.2008.09.019.
   PubMedGoogle Scholar
• Pufall MA, Graves BJ. 2002. Autoinhibitory domains: modular effectors of cellular regulation. Annu. Rev. Cell Dev. Biol. 18:421–462. http://dx.doi.org/10.1146/annurev.cellbio.18.031502.133614.
   PubMedGoogle Scholar
• Boggon TJ, Eck MJ. 2004. Structure and regulation of Src family kinases. Oncogene 23:7918–7927. http://dx.doi.org/10.1038/sj.onc.1208081.
   PubMed Web of Science ®Google Scholar
• Rubin SM, Gall AL, Zheng N, Pavletich NP. 2005. Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release. Cell 123:1093–1106. http://dx.doi.org/10.1016/j.cell.2005.09.044.
   PubMed Web of Science ®Google Scholar
• Wu S, Chen L, Becker A, Schonbrunn E, Chen J. 2012. Casein kinase 1alpha regulates an MDMX intramolecular interaction to stimulate p53 binding. Mol. Cell. Biol. 32:4821–4832. http://dx.doi.org/10.1128/MCB.00851-12.
   PubMedGoogle Scholar
• Bista M, Petrovich M, Fersht AR. 2013. MDMX contains an autoinhibitory sequence element. Proc. Natl. Acad. Sci. U. S. A. 110:17814–17819. http://dx.doi.org/10.1073/pnas.1317398110.
   PubMedGoogle Scholar
• Dolezelova P, Cetkovska K, Vousden KH, Uldrijan S. 2012. Mutational analysis reveals a dual role of Mdm2 acidic domain in the regulation of p53 stability. FEBS Lett. 586:2225–2231. http://dx.doi.org/10.1016/j.febslet.2012.05.034.
   PubMedGoogle Scholar
• Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. 1996. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274:948–953. http://dx.doi.org/10.1126/science.274.5289.948.
   PubMed Web of Science ®Google Scholar
• Yu GW, Allen MD, Andreeva A, Fersht AR, Bycroft M. 2006. Solution structure of the C4 zinc finger domain of HDM2. Protein Sci. 15:384–389. http://dx.doi.org/10.1110/ps.051927306.
   PubMedGoogle Scholar
• Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL. 2008. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ. 15:841–848. http://dx.doi.org/10.1038/sj.cdd.4402309.
   PubMed Web of Science ®Google Scholar
• Wade M, Li YC, Wahl GM. 2013. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat. Rev. Cancer 13:83–96. http://dx.doi.org/10.1038/nrc3430.
   PubMed Web of Science ®Google Scholar
• Yang Y, Ludwig RL, Jensen JP, Pierre SA, Medaglia MV, Davydov IV, Safiran YJ, Oberoi P, Kenten JH, Phillips AC, Weissman AM, Vousden KH. 2005. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 7:547–559. http://dx.doi.org/10.1016/j.ccr.2005.04.029.
   PubMed Web of Science ®Google Scholar
• Herman AG, Hayano M, Poyurovsky MV, Shimada K, Skouta R, Prives C, Stockwell BR. 2011. Discovery of Mdm2-MdmX E3 ligase inhibitors using a cell-based ubiquitination assay. Cancer Discov. 1:312–325. http://dx.doi.org/10.1158/2159-8290.CD-11-0104.
   PubMedGoogle Scholar
• Komarov PG, Komarova EA, Kondratov RV, Christov-Tselkov K, Coon JS, Chernov MV, Gudkov AV. 1999. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285:1733–1737. http://dx.doi.org/10.1126/science.285.5434.1733.
   PubMed Web of Science ®Google Scholar