Structural and Functional Comparison of the RING Domains of Two p53 E3 Ligases, Mdm2 and Pirh2
Open accessAbstract
The tumor suppressor p53 maintains genome stability and prevents malignant transformation by promoting cell cycle arrest and apoptosis. Both Mdm2 and Pirh2 have been shown to ubiquitylate p53 through their RING domains, thereby targeting p53 for proteasomal degradation. Using structural and functional analyses, here we show that the Pirh2 RING domain differs from the Mdm2 RING domain in its oligomeric state, surface charge distribution, and zinc coordination scheme. Pirh2 also possesses weaker E3 ligase activity toward p53 and directs ubiquitin to different residues on p53. NMR and mutagenesis studies suggest that whereas Pirh2 and Mdm2 share a conserved E2 binding site, the seven C-terminal residues of the Mdm2 RING directly contribute to Mdm2 E3 ligase activity, a feature unique to Mdm2 and absent in the Pirh2 RING domain. This comprehensive analysis of the Pirh2 and Mdm2 RING domains provides structural and mechanistic insight into p53 regulation by its E3 ligases.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Multiple E2 enzymes can attach ubiquitin to p53 in vitro.
“Although several E2s can transfer ubiquitin to p53 in vitro 118,119”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [118]
Cites
The PyMOL Molecular Graphics System
DeLano, W. L. (2002) · Medical Entomology and Zoology · Cited by 18,147 · see citing works
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,994 · see citing works
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693 · see citing works
MOLMOL: A program for display and analysis of macromolecular structures
Koradi, R., Billeter, M., & Kurt Wüthrich, A. (1996) · Journal of Molecular Graphics · doi:10.1016/0263-7855(96)00009-4 · Cited by 7,163 · see citing works
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661 · see citing works
TANDEM: matching proteins with tandem mass spectra
Craig, R., & Beavis, R. C. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth092 · Cited by 2,553 · see citing works
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M. (1993) · Cell · doi:10.1016/0092-8674(93)90384-3 · Cited by 2,387 · see citing works
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206 · see citing works
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
Honda, R., Tanaka, H., & Yasuda, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01480-4 · Cited by 1,951 · see citing works
The program XEASY for computer-supported NMR spectral analysis of biological macromolecules
Bartels, C., Xia, T.-H., Billeter, M., Güntert, P., & Kurt Wüthrich, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00417486 · Cited by 1,636 · see citing works
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,472 · see citing works
Dali: a network tool for protein structure comparison
Holm, L., & Sander, C. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89105-7 · Cited by 1,462 · see citing works
Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
de Oca Luna, R. M., Wagner, D. S., & Lozano, G. (1995) · Nature · doi:10.1038/378203a0 · Cited by 1,420 · see citing works
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas
Toledo, F., & Wahl, G. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2012 · Cited by 1,286 · see citing works
Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A. (1995) · Nature · doi:10.1038/378206a0 · Cited by 1,280 · see citing works
Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53
Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H., & Weissman, A. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8945 · Cited by 1,044 · see citing works
Structure of a c-Cbl–UbcH7 Complex
Zheng, N., Wang, P., Jeffrey, P. D., & Pavletich, N. P. (2000) · Cell · doi:10.1016/s0092-8674(00)00057-x · Cited by 839 · see citing works
Acetylation Is Indispensable for p53 Activation
Tang, Y., Zhao, W., Chen, Y., Zhao, Y., & Gu, W. (2008) · Cell · doi:10.1016/j.cell.2008.03.025 · Cited by 838 · see citing works
A common open representation of mass spectrometry data and its application to proteomics research
Pedrioli, P. G. A., Eng, J. K., Hubley, R. M., Vogelzang, M., Deutsch, E. W., Raught, B., Pratt, B. S., Nilsson, E. J., Angeletti, R. H., Apweiler, R., et al. (2004) · Nature Biotechnology · doi:10.1038/nbt1031 · Cited by 782 · see citing works
Self-citationArsenic degrades PML or PML–RARα through a SUMO-triggered RNF4/ubiquitin-mediated pathway
Lallemand-Breitenbach, V., Jeanne, M., Benhenda, S., Nasr, R., Lei, M., Pérès, L., Zhou, J., Zhu, J., Raught, B., & de Thé, H. (2008) · Nature Cell Biology · doi:10.1038/ncb1717 · Cited by 726 · see citing works
Self-citationPirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation
Leng, R. P., Lin, Y., Ma, W., Wu, H., Lemmers, B., Chung, S., Parant, J. M., Lozano, G., Hakem, R., & Benchimol, S. (2003) · Cell · doi:10.1016/s0092-8674(03)00193-4 · Cited by 717 · see citing works
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507493103 · Cited by 708 · see citing works
The ubiquitin ligase COP1 is a critical negative regulator of p53
Dornan, D., Wertz, I. E., Shimizu, H., Arnott, D. P., Frantz, G. D., Dowd, P., Rourke, K. O., Koeppen, H., & Dixit, V. M. (2004) · Nature · doi:10.1038/nature02514 · Cited by 700 · see citing works
ARF-BP1/Mule Is a Critical Mediator of the ARF Tumor Suppressor
Chen, D., Kon, N., Li, M., Zhang, W., Qin, J., & Gu, W. J. (2005) · Cell · doi:10.1016/j.cell.2005.03.037 · Cited by 539 · see citing works
Parant, J., Chavez-Reyes, A., Little, N. A., Yan, W., Reinke, V., Jochemsen, A. G., & Lozano, G. (2001) · Nature Genetics · doi:10.1038/ng714 · Cited by 517 · see citing works
Banks, L., Matlashewski, G., & Crawford, L. (1986) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1986.tb09919.x · Cited by 505 · see citing works
Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.
Brzović, P. S., Rajagopal, P., Hoyt, D. W., King, M., & Klevit, R. E. (2001) · Nature Structural Biology · doi:10.1038/nsb1001-833 · Cited by 494 · see citing works
Transcription-independent pro-apoptotic functions of p53
Moll, U. M., Wolff, S., Speidel, D., & Deppert, W. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.007 · Cited by 468 · see citing works
Structure and E3‐ligase activity of the Ring–Ring complex of Polycomb proteins Bmi1 and Ring1b
Buchwald, G., van der Stoop, P. P. M., Weichenrieder, O., Anastassis Perrakis, A., van Lohuizen, M., & Sixma, T. K. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601144 · Cited by 438 · see citing works
Multiple C-Terminal Lysine Residues Target p53 for Ubiquitin-Proteasome-Mediated Degradation
Rodríguez, M. S., Desterro, J. M. P., Laı́n, S., Lane, D. P., & Hay, R. T. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8458-8467.2000 · Cited by 386 · see citing works
Three-dimensional structure of ectatomin from Ectatomma tuberculatum ant venom
Nolde, D. E., Sobol, A. G., Pluzhnikov, K. A., Grishin, E. V., & Arseniev, A. S. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00227465 · Cited by 363 · see citing works
Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4
Marine, J.-C., Francoz, S., Maetens, M., Wahl, G., Toledo, F., & Lozano, G. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401912 · Cited by 352 · see citing works
E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages
Christensen, D. E., Brzovic, P. S., & Klevit, R. E. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1295 · Cited by 351 · see citing works
Borden, K. L. B., Boddy, M. N., Lally, J., O’Reilly, N., Martin, S. R., Howe, K. M., Solomon, E., & Freemont, P. S. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07139.x · Cited by 328 · see citing works
Linke, K., Mace, P. D., Smith, C. A., Vaux, D. L., Silke, J., & Day, C. L. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402309 · Cited by 288 · see citing works
Cytoplasmic destruction of p53 by the endoplasmic reticulum‐resident ubiquitin ligase ‘Synoviolin’
Yamasaki, S., Yagishita, N., Sasaki, T., Nakazawa, M., Kato, Y., Yamadera, T., Bae, E.-K., Toriyama, S., Ikeda, R., Zhang, L., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601490 · Cited by 275 · see citing works
Mutual Dependence of MDM2 and MDMX in Their Functional Inactivation of p53
Gu, J., Kawai, H., Nie, L., Kitao, H., Wiederschain, D., Jochemsen, A. G., Parant, J. M., Lozano, G., & Yuan, Z.-M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200150200 · Cited by 265 · see citing works
Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells <i>in vivo</i>
Francoz, S., Froment, P., Bogaerts, S., De Clercq, S., Maetens, M., Doumont, G., Bellefroid, E., & Marine, J.-C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508476103 · Cited by 260 · see citing works
Structure of a Bmi-1-Ring1B Polycomb Group Ubiquitin Ligase Complex
Li, Z., Cao, R., Wang, M., Myers, M. P., Zhang, Y., & Xu, R.-M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602461200 · Cited by 246 · see citing works
Cam, L. L., Linares, L. K., Paul, C., Julien, E., Lacroix, M., Hatchi, E., Triboulet, R., Bossis, G., Shmueli, A., Rodríguez, M. S., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.031 · Cited by 241 · see citing works
C-Terminal Ubiquitination of p53 Contributes to Nuclear Export
Lohrum, M. A. E., Woods, D. B., Ludwig, R. L., Bálint, É., & Vousden, K. H. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.24.8521-8532.2001 · Cited by 237 · see citing works
Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms
Stad, R., Little, N. A., Xirodimas, D. P., Frenk, R., van der Eb, A. J., Lane, D. P., Saville, M. K., & Jochemsen, A. G. (2001) · The EMBO Reports · doi:10.1093/embo-reports/kve227 · Cited by 234 · see citing works
Marine, J.-C. W., Dyer, M. A., & Jochemsen, A. G. (2007) · Journal of Cell Science · doi:10.1242/jcs.03362 · Cited by 228 · see citing works
MdmX Protects p53 from Mdm2-Mediated Degradation
Jackson, M. W., & Berberich, S. J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.3.1001-1007.2000 · Cited by 211 · see citing works
Poyurovsky, M. V., Priest, C., Kentsis, A., Borden, K. L., Pan, Z., Pavletich, N., & Prives, C. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601465 · Cited by 203 · see citing works
Mace, P. D., Linke, K., Feltham, R., Schumacher, F., Smith, C. A., Vaux, D. L., Silke, J., & Day, C. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804753200 · Cited by 171 · see citing works
An essential function of the extreme C-terminus of MDM2 can be provided by MDMX
Uldrijan, S., Pannekoek, W., & Vousden, K. H. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601469 · Cited by 170 · see citing works
BRCA1 RING Domain Cancer-predisposing Mutations
Brzović, P. S., Meza, J. E., King, M., & Klevit, R. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106551200 · Cited by 133 · see citing works
Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53
Kostic, M., Matt, T., Martinez-Yamout, M. A., Dyson, H. J., & Wright, P. E. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.08.027 · Cited by 128 · see citing works
Dominguez, C., Bonvin, A. M. J. J., Winkler, G. S., van Schaik, F. M. A., Timmers, H. T. M., & Boelens, R. (2004) · Structure · doi:10.1016/j.str.2004.03.004 · Cited by 124 · see citing works
Global Map of SUMO Function Revealed by Protein-Protein Interaction and Genetic Networks
Makhnevych, T., Sydorskyy, Y., Xin, X., Srikumar, T., Vizeacoumar, F. J., Jeram, S. M., Li, Z., Bahr, S., Andrews, B., Boone, C. M., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2008.12.025 · Cited by 121 · see citing works
Self-citationMolecular basis of Pirh2-mediated p53 ubiquitylation
Sheng, Y., Laister, R. C., Lemak, A. S., Wu, B., Tai, E., Duan, S., Lukin, J. A., Sunnerhagen, M., Srisailam, S., Karra, M., et al. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1521 · Cited by 116 · see citing works
Self-citationRegulation of p53 Localization and Activity by Ubc13
Laine, A. M., Topisirović, I., Zhai, D., Reed, J. C., Borden, K. L. B., & Ronai, Z. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01156-06 · Cited by 101 · see citing works
Expression of Pirh2, a Newly Identified Ubiquitin Protein Ligase, in Lung Cancer
Duan, W., Gao, L., Druhan, L. J., Zhu, W., Morrison, C., Otterson, G. A., & Villalona-Calero, M. A. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh292 · Cited by 96 · see citing works
Logan, I. R., Gaughan, L., McCracken, S. R., Sapountzi, V., Leung, H. Y., & Robson, C. N. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00147-06 · Cited by 88 · see citing works
The RING domain of Mdm2 can inhibit cell proliferation.
Dang, J., Kuo, M.-L., Eischen, C. M., Stepanova, L., Sherr, C. J., & Roussel, M. F. (2002) · PubMed · Cited by 86 · see citing works
p53's Believe It or Not: Lessons on Transcription-Independent Death
Chipuk, J. E., & Green, D. R. (2003) · Journal of Clinical Immunology · doi:10.1023/a:1025365432325 · Cited by 81 · see citing works
Mdmx and Mdm2: Brothers in Arms?
Marine, J., & Jochemsen, A. G. (2004) · Cell Cycle · doi:10.4161/cc.3.7.998 · Cited by 77 · see citing works
A Second p53 Binding Site in the Central Domain of Mdm2 Is Essential for p53 Ubiquitination
Ma, J., Martin, J. D., Zhang, H., Auger, K. R., Ho, T. F., Kirkpatrick, R. B., Grooms, M. H., Johanson, K., Tummino, P. J., Copeland, A. R. A., et al. (2006) · Biochemistry · doi:10.1021/bi060661u · Cited by 68 · see citing works
Control of p53 multimerization by Ubc13 is JNK-regulated
Topisirović, I., Gutierrez, G. J., Chen, M., Appella, E., Borden, K. L. B., & Ronai, Z. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900596106 · Cited by 56 · see citing works
Lyakhovich, A., & Shekhar, M. P. V. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.7.2463-2475.2003 · Cited by 49 · see citing works
Duan, W., Gao, L., Wu, X., Zhang, Y., Otterson, G. A., & Villalona-Calero, M. A. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.07.005 · Cited by 38 · see citing works
Solution Structure of the Ubiquitin-conjugating Enzyme UbcH5B
Houben, K., Dominguez, C., van Schaik, F. M. A., Timmers, H. T. M., Bonvin, A. M. J. J., & Boelens, R. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.09.054 · Cited by 33 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
MDM2, MDMX and p53 in oncogenesis and cancer therapy
Wade, M., Li, Y.-C., & Wahl, G. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3430 · Cited by 1,279 · see citing works
Regulating tumor suppressor genes: post-translational modifications
Chen, L., Liu, S., & Tao, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0196-9 · Cited by 449 · see citing works
Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System
Kocatürk, N. M., & Gözüaçık, D. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00128 · Cited by 415 · see citing works
Ma‐Lauer, Y., Carbajo-Lozoya, J., Hein, M. Y., Müller, M. A., Deng, W., Lei, J., Meyer, B., Kusov, Y., von Brunn, B., Bairad, D. R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603435113 · Cited by 214 · see citing works
RINGs hold the key to ubiquitin transfer
Budhidarmo, R., Nakatani, Y., & Day, C. L. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.11.001 · Cited by 206 · see citing works
The role of ubiquitin modification in the regulation of p53
Hock, A. K., & Vousden, K. H. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.05.022 · Cited by 168 · see citing works
Espinosa, A., Hennig, J., Ambrosi, A., Anandapadmanaban, M., Abelius, M. S., Sheng, Y., Nyberg, F., Arrowsmith, C. H., Sunnerhagen, M., & Wahren‐Herlenius, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.241786 · Cited by 90 · see citing works
Self-citationMendoza, M. J., Mandani, G., & Momand, J. A. (2013) · BioMolecular Concepts · doi:10.1515/bmc-2013-0027 · Cited by 86 · see citing works
Lienlaf, M., Hayashi, F., Nunzio, F. D., Tochio, N., Kigawa, T., Yokoyama, S., & Diaz‐Griffero, F. (2011) · Journal of Virology · doi:10.1128/jvi.00497-11 · Cited by 86 · see citing works
E2 Conjugating Enzyme Selectivity and Requirements for Function of the E3 Ubiquitin Ligase CHIP
Soss, S. E., Yue, Y., Dhe‐Paganon, S., & Chazin, W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.224006 · Cited by 84 · see citing works
Self-citationTargeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies
Shen, J., Wang, Q., Mao, Y., Gao, W., & Duan, S. (2023) · MedComm · doi:10.1002/mco2.288 · Cited by 66 · see citing works
Self-citationMDMX contains an autoinhibitory sequence element
Biśta, M., Petrovich, M., & Fersht, A. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317398110 · Cited by 57 · see citing works
Yan, W., Jung, Y.-S., Zhang, Y., & Chen, X. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103497 · Cited by 51 · see citing works
Zinc deficiency causes neural tube defects through attenuation of p53 ubiquitylation
Li, H., Zhang, J., & Niswander, L. A. (2018) · Development · doi:10.1242/dev.169797 · Cited by 52 · see citing works
Marcar, L., Ihrig, B., Hourihan, J. M., Bray, S. E., Quinlan, P., Jordan, L. B., Thompson, A. M., Hupp, T. R., & Meek, D. W. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127713 · Cited by 42 · see citing works
Uddin, M. A., & Barabutis, N. (2020) · DNA repair · doi:10.1016/j.dnarep.2020.102952 · Cited by 35 · see citing works
Doleželová, P., Cetkovská, K., Vousden, K. H., & Uldrijan, S. (2012) · Cell Cycle · doi:10.4161/cc.11.5.19445 · Cited by 33 · see citing works
Regulation of transcriptional activators by DNA-binding domain ubiquitination
Landré, V., Revi, B., Gil-Mir, M., Verma, C. S., Hupp, T. R., Gilbert, N., & Ball, K. L. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.42 · Cited by 32 · see citing works
It Takes 15 to Tango: Making Sense of the Many Ubiquitin Ligases of p53
Love, I. M., & Grossman, S. R. (2012) · Genes & Cancer · doi:10.1177/1947601912455198 · Cited by 28 · see citing works
Pan, M., & Blattner, C. (2021) · Cancers · doi:10.3390/cancers13040745 · Cited by 27 · see citing works
Yan, W., Scoumanne, A., Jung, Y.-S., Xu, E., Zhang, J., Zhang, Y., Ren, C., Sun, P., & Chen, X. (2016) · Genes & Development · doi:10.1101/gad.271890.115 · Cited by 21 · see citing works
Opazo, C. M., Lotan, A., Xiao, Z., Zhang, B., Greenough, M. A., Lim, C. M., Trytell, H., Ramírez, A., Ukuwela, A. A., Mawal, C. H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.15.431211 · Cited by 21 · see citing works
Hinokiflavone Inhibits MDM2 Activity by Targeting the MDM2-MDMX RING Domain
Ilic, V. K., Egorova, O., Tsang, E., Gatto, M., Wen, Y., Zhao, Y., & Sheng, Y. (2022) · Biomolecules · doi:10.3390/biom12050643 · Cited by 20 · see citing works
Self-citationMDM2 Mediates Nonproteolytic Polyubiquitylation of the DEAD-Box RNA Helicase DDX24
Yamauchi, T., Nishiyama, M., Moroishi, T., Yumimoto, K., & Nakayama, K. I. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00320-14 · Cited by 20 · see citing works
Concepts in MDM2 Signaling: Allosteric Regulation and Feedback Loops
Ponnuswamy, A., Hupp, T. R., & Fåhræus, R. (2012) · Genes & Cancer · doi:10.1177/1947601912454140 · Cited by 18 · see citing works
Recognition of an Ala-rich C-degron by the E3 ligase Pirh2
Wang, X., Li, Y., Yan, X., Yang, Q., Zhang, B., Zhang, Y., Yuan, X., Jiang, C., Chen, D., Liu, Q., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38173-6 · Cited by 14 · see citing works
A site-directed mutagenesis study of the MdmX RING domain
Egorova, O., & Sheng, Y. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.04.065 · Cited by 10 · see citing works
Self-citationZeinab, R. A., Wu, H., Sergi, C. M., & Leng, R. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082803 · Cited by 7 · see citing works
RetractedProteasomal control of transcription factors: mechanisms, regulation and dysregulation
Larsen, F. B., Kragelund, B. B., Lindorff‐Larsen, K., Heidarsson, P. O., & Hartmann‐Petersen, R. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06103-6 · Cited by 6 · see citing works
Mohibi, S., Zhang, J., Chen, M., & Chen, X. (2021) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-21-0239 · Cited by 6 · see citing works
Niazi, S., & Purohit, M. N. (2015) · MedChemComm · doi:10.1039/c5md00319a · Cited by 5 · see citing works
p53 regulation by ubiquitin and ubiquitin-like modifications
Wang, Y., Zhang, C., Wang, J., & Liu, J. (2022) · Genome Instability & Disease · doi:10.1007/s42764-022-00067-0 · Cited by 5 · see citing works
Abdelrahman, A. E., Salem, A., Attar, A. Z. A., Elsebai, E. A., Samy, W. M., Ibrahim, M. A., & Ibrahim, H. (2022) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000001073 · Cited by 4 · see citing works
George, M., Masamba, P., Iwalokun, B. A., & Kappo, A. P. (2023) · PubMed Central · Cited by 3 · see citing works
The Role of Pirh2 E3 Ligases in Ubiquitination and p73 Regulation
Abou Zeinab, R. M. (2015) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3610vx4f · Cited by 1 · see citing works
Dissecting the Interaction between p53 and TRIM24
Duncan, A. D. (2011) · Digital Commons-TMC (Texas Medical Center)
DigitalCommons@Th e Texas Medical Center
Gsbs, U., & Hong, J. Y. (2011)
Structural and Functional Characterization of the Human Mdm2 and MdmX RING Domains
Egorova, O. (2014) · YorkSpace (York University)
An Integrated Structure-based Approach for the Development of MDM2 inhibitors
Sheng, Y. (2021) · International Electronic Conference on Cancers (IECC) · doi:10.3390/iecc2021-09208
Self-citationThe tumour suppressor p53 as a supporter of DNA replication
Klusmann, I. (2018) · doi:10.53846/goediss-7143
RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma
Zhang, J.-F., Li, L.-T., Yang, Y.-Y., Zhang, S.-C., Gao, C., Zhu, X., Xin, H., & Li, X. (2026) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-026-00940-w
- Authors
- Shloush, J., Vlassov, J. E., Engson, I., Duan, S., Saridakis, V., Dhe-paganon, S., Raught, B., Sheng, Y., & Arrowsmith, C. H.
- Affiliations
- York University (CA)
- Corresponding author
- Sheng, Yi
- Arrowsmith, Cheryl H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 286
- Issue
- 6
- Pages
- 4796-4808
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3039342
- OpenAlex
- W2074600331
- Cited by
- 42
- References
- 63
- Citations by year
- 2026: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- p53, MDM2, Pirh2, RING domain, E3 ubiquitin ligase, p53 ubiquitination, proteasomal degradation, zinc coordination, oligomeric state, surface charge distribution, E2 binding sites, tumor suppressor regulation
- MeSH terms
- Binding Sites, Humans, Structure-Activity Relationship, Tumor Suppressor Protein p53, Mutagenesis, Nuclear Magnetic Resonance, Biomolecular, Ubiquitin-Protein Ligases, Proto-Oncogene Proteins c-mdm2, RING Finger Domains, Protein Multimerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review