Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2
Open accessAbstract
The mdm2 and mdmx oncogenes play essential yet nonredundant roles in synergistic inactivatiosn of p53. However, the biochemical mechanism by which Mdmx synergizes with Mdm2 to inhibit p53 function remains obscure. Here we demonstrate that, using nonphosphorylatable mutants of Mdmx, the cooperative inhibition of p53 by Mdmx and Mdm2 was associated with cytoplasmic localization of p53, and with an increase of the interaction of Mdmx to p53 and Mdm2 in the cytoplasm. In addition, the Mdmx mutant cooperates with Mdm2 to induce ubiquitination of p53 at C-terminal lysine residues, and the integrity of the C-terminal lysines was partly required for the cooperative inhibition. The expression of subcellular localization mutants of Mdmx revealed that subcellular localization of Mdmx dictated p53 localization, and that cytoplasmic Mdmx tethered p53 in the cytoplasm and efficiently inhibited p53 activity. RNAi-mediated inhibition of Mdmx or introduction of the nuclear localization mutant of Mdmx reduced cytoplasmic retention of p53 in neuroblastoma cells, in which cytoplasmic sequestration of p53 is involved in its inactivation. Our data indicate that cytoplasmic tethering of p53 mediated by Mdmx contributes to p53 inactivation in some types of cancer cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Mdm2 promotes translocation of p53 from the nucleus to the cytoplasm, and Mdmx may modulate this process.
“Interestingly, Mdm2 has been reported to promote translocation of p53 from the nucleus to the cytoplasm, and Mdmx may modulate this process [4].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · see citing works
p53: puzzle and paradigm.Preprint
Ko, L. J., & Prives, C. L. (1996) · Genes & Development · doi:10.1101/gad.10.9.1054 · Cited by 2,338 · 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
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
Decision making by p53: life, death and cancer
Oren, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401183 · Cited by 1,063 · see citing works
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804 · see citing works
The p53–Mdm2 module and the ubiquitin system
Michael, D., & Oren, M. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044-579x(02)00099-8 · Cited by 759 · see citing works
A dynamic role of HAUSP in the p53-Mdm2 pathway
Li, M., Brooks, C. L., Kon, N., & Gu, W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00157-1 · Cited by 679 · see citing works
Inactivation of the p53 pathway in retinoblastoma
Laurie, N. A., Donovan, S. L., Shih, C.-S., Zhang, J., Mills, N., Fuller, C., Teunisse, A., Lam, S., Ramos, Y., Mohan, A., et al. (2006) · Nature · doi:10.1038/nature05194 · Cited by 595 · see citing works
Mdm2-Mediated NEDD8 Conjugation of p53 Inhibits Its Transcriptional Activity
Xirodimas, D. P., Saville, M. K., Bourdon, J.-C., Hay, R. T., & Lane, D. P. (2004) · Cell · doi:10.1016/j.cell.2004.06.016 · Cited by 570 · see citing works
Xiang, Y., Zheng, Q., Jia, B., Huang, G., Xie, C., Pan, J., & Wang, J. (2006) · Cell Biology International · doi:10.1016/j.cellbi.2006.11.012 · Cited by 429 · see citing works
Moll, U. M., LaQuaglia, M. P., Bénard, J., & RIOU, G. F. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4407 · Cited by 426 · see citing works
HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
Linares, L. K., Hengstermann, A., Ciechanover, A., Müller, S., & Scheffner, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2030930100 · Cited by 361 · 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
MDM2 interacts with MDMX through their RING finger domains
Tanimura, S., Ohtsuka, S., Mitsui, K., Shirouzu, K., Yoshimura, A., & Ohtsubo, M. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00254-9 · Cited by 324 · see citing works
Danovi, D., Meulmeester, E., Pasini, D., Migliorini, D., Capra, M., Frenk, R., de Graaf, P., Francoz, S., Gasparini, P., Gobbi, A., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5835-5843.2004 · Cited by 310 · see citing works
Stabilization of the MDM2 Oncoprotein by Interaction with the Structurally Related MDMX Protein
Sharp, D. A., Kratowicz, S. A., Sank, M. J., & George, D. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.53.38189 · Cited by 286 · 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
MDM2 and MDM4: p53 regulators as targets in anticancer therapy
Toledo, F., & Wahl, G. M. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.03.022 · Cited by 261 · see citing works
Meulmeester, E., Maurice, M. M., Boutell, C., Teunisse, A. F. A. S., Ovaa, H., Abraham, T. E., Dirks, R. W., & Jochemsen, A. G. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.04.024 · Cited by 260 · see citing works
Self-citationATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage
Chen, L., Gilkes, D. M., Pan, Y., Lane, W. S., & Chen, J. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600812 · Cited by 260 · 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
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
Toledo, F., Krummel, K. A., Lee, C. J., Liu, C.-W., Rodewald, L.-W., Tang, M., & Wahl, G. M. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.014 · Cited by 199 · see citing works
Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage
Pereg, Y., Shkedy, D., de Graaf, P., Meulmeester, E., Edelson-Averbukh, M., Salek, M., Biton, S., Teunisse, A. F. A. S., Lehmann, W. D., Jochemsen, A. G., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408595102 · Cited by 181 · see citing works
Self-citationJimenez, G. S., Khan, S. H., Stommel, J. M., & Wahl, G. M. (1999) · Oncogene · doi:10.1038/sj.onc.1203013 · Cited by 176 · 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
Okamoto, K., Kashima, K., Pereg, Y., Ishida, M., Yamazaki, S., Nota, A., Teunisse, A., Migliorini, D., Kitabayashi, I., Marine, J.-C., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9608-9620.2005 · Cited by 129 · see citing works
14‐3‐3γ binds to MDMX that is phosphorylated by UV‐activated Chk1, resulting in p53 activation
Jin, Y., Dai, M., Lu, S. Z., Xu, Y., Luo, Z., Zhao, Y., & Lu, H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601010 · Cited by 113 · see citing works
Identification of p53 Sequence Elements That Are Required for MDM2-Mediated Nuclear Export
Gu, J., Nie, L., Wiederschain, D., & Yuan, Z.-M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.24.8533-8546.2001 · Cited by 100 · see citing works
Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export
Shinozaki, T., Nota, A., Taya, Y., & Okamoto, K. (2003) · Oncogene · doi:10.1038/sj.onc.1207176 · Cited by 93 · see citing works
Differential Roles of ATM- and Chk2-Mediated Phosphorylations of Hdmx in Response to DNA Damage
Pereg, Y., Lam, S., Teunisse, A., Biton, S., Meulmeester, E., Mittelman, L., Buscemi, G., Okamoto, K., Taya, Y., Shiloh, Y., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00562-06 · Cited by 93 · see citing works
Nuclear exclusion of p53 in a subset of tumors requires MDM2 function
Lu, W., Pochampally, R. R., Chen, L., Chomnawang, M. T., Wang, Y., & Chen, J. (2000) · Oncogene · doi:10.1038/sj.onc.1203262 · Cited by 90 · see citing works
Phosphorylation of MDMX Mediated by Akt Leads to Stabilization and Induces 14-3-3 Binding
Lopez-Pajares, V., Kim, M. M., & Yuan, Z.-M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710030200 · Cited by 79 · see citing works
Singh, R. K., Iyappan, S., & Scheffner, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610879200 · Cited by 69 · see citing works
MDM2 Mediated Nuclear Exclusion of p53 Attenuates Etoposide-Induced Apoptosis in Neuroblastoma Cells
Rodrı́guez-López, A. M., Xenaki, D., Eden, T. O. B., Hickman, J. A., & Chresta, C. M. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.1.135 · Cited by 56 · see citing works
Hyperubiquitylation of wild-type p53 contributes to cytoplasmic sequestration in neuroblastoma
Becker, K., Marchenko, N. D., Maurice, M. M., & Moll, U. M. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402126 · Cited by 53 · see citing works
Shmueli, A., & Oren, M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(03)00529-x · Cited by 51 · see citing works
p53: more research and more questions
Braithwaite, A. W., & Prives, C. L. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401938 · Cited by 40 · see citing works
Coutts, A. S., & Thangue, N. B. L. (2007) · Cell Cycle · doi:10.4161/cc.6.7.4086 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The p53 orchestra: Mdm2 and Mdmx set the tone
Wade, M., Wang, Y. V., & Wahl, G. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.009 · Cited by 450 · see citing works
A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53
Bernal, F., Wade, M. R., Godes, M., Davis, T. N., Whitehead, D. G., Kung, A. L., Wahl, G. M., & Walensky, L. D. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.024 · Cited by 284 · see citing works
In Vivo Activation of the p53 Tumor Suppressor Pathway by an Engineered Cyclotide
Ji, Y., Majumder, S., Millard, M., Borra, R., Bi, T., Elnagar, A. Y., Neamati, N., Shekhtman, A. G., & Camarero, J. A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja405108p · Cited by 233 · see citing works
NSUN6 is a human RNA methyltransferase that catalyzes formation of m 5 C72 in specific tRNAs
Haag, S., Warda, A. S., Kretschmer, J., Günnigmann, M. A., Höbartner, C., & Bohnsack, M. T. (2015) · RNA · doi:10.1261/rna.051524.115 · Cited by 188 · see citing works
MdmX Protein Is Essential for Mdm2 Protein-mediated p53 Polyubiquitination
Wang, X., Wang, J., & Jiang, X. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.213868 · Cited by 115 · see citing works
Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope
Zafar, A., Wang, W., Liu, G., Xian, W., McKeon, F., Zhou, J., & Zhang, R. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.09.023 · Cited by 107 · see citing works
MicroRNA-34a Modulates MDM4 Expression via a Target Site in the Open Reading Frame
Mandke, P., Wyatt, N., Fraser, J., Bates, B., Berberich, S. J., & Markey, M. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042034 · Cited by 90 · see citing works
Medicinal Chemistry Strategies to Disrupt the p53–MDM2/MDMX Interaction
Lemos, A., Leão, M., Soares, J., Palmeira, A., Pinto, M. M. M., Saraiva, L., & Sousa, M. E. (2016) · Medicinal Research Reviews · doi:10.1002/med.21393 · Cited by 83 · see citing works
Androgen induces G3BP2 and SUMO-mediated p53 nuclear export in prostate cancer
Ashikari, D., Takayama, K., Tanaka, T., Suzuki, Y., Obinata, D., Fujimura, T., Urano, T., Takahashi, S., & Inoue, S. (2017) · Oncogene · doi:10.1038/onc.2017.225 · Cited by 80 · see citing works
Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase
Okamoto, K., Taya, Y., & Nakagama, H. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.07.021 · Cited by 76 · see citing works
Self-citationEscape from p53-mediated tumor surveillance in neuroblastoma: switching off the p14ARF-MDM2-p53 axis
Maerken, T. V., Vandesompele, J., Rihani, A., Paepe, A. D., & Speleman, F. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.138 · Cited by 70 · see citing works
Tollini, L. A., Jin, A., Park, J., & Zhang, Y. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.06.006 · Cited by 66 · see citing works
p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance
Chen, L., & Tweddle, D. A. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00173 · Cited by 43 · see citing works
Swetzig, W. M., Wang, J., & Das, G. M. (2016) · Oncotarget · doi:10.18632/oncotarget.7533 · Cited by 42 · see citing works
MDMX Recruits UbcH5c to Facilitate MDM2 E3 Ligase Activity and Subsequent p53 Degradation In Vivo
Yang, J., Jin, A., Han, J., Chen, X., Zheng, J., & Zhang, Y. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0790 · Cited by 39 · see citing works
High Mdm4 levels suppress p53 activity and enhance its half-life in acute myeloid leukaemia
Tan, B. X., Khoo, K. H., Lim, T. M., & Lane, D. P. (2013) · Oncotarget · doi:10.18632/oncotarget.1559 · Cited by 34 · see citing works
Acar, H., Samaeekia, R., Schnorenberg, M. R., Sasmal, D. K., Huang, J., Tirrell, M., & LaBelle, J. L. (2017) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.7b00364 · Cited by 28 · see citing works
Giustiniano, M., Daniele, S., Pelliccia, S., Pietra, V. L., Pietrobono, D., Brancaccio, D., Cosconati, S., Messere, A., Giuntini, S., Cerofolini, L., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00912 · Cited by 25 · see citing works
Markey, M. P. (2010) · Frontiers in bioscience · doi:10.2741/3780 · Cited by 24 · see citing works
A novel mechanism of crosstalk between the p53 and NFκB pathways
Heyne, K., Winter, C., Gerten, F., Schmidt, C., & Roemer, K. (2013) · Cell Cycle · doi:10.4161/cc.25495 · Cited by 22 · see citing works
MDM2 binds and inhibits vitamin D receptor
Heyne, K., Heil, T. C., Bette, B., Reichrath, J., & Roemer, K. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1044176 · Cited by 20 · see citing works
Transcriptional repressor NIR interacts with the p53-inhibiting ubiquitin ligase MDM2
Heyne, K., Förster, J., Schüle, R., & Roemer, K. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1371 · Cited by 19 · see citing works
Palomares, A. R., Castillo-Domínguez, A. A., Ruiz‐Galdón, M., Rodriguez‐Wallberg, K. A., & Reyes‐Engel, A. (2021) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-021-02324-9 · Cited by 18 · see citing works
Hav, M., Libbrecht, L. J., Ferdinande, L., Pattyn, P., Laurent, S., Peeters, M., Praet, M. M., & Pauwels, P. (2010) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-010-1012-7 · Cited by 18 · see citing works
Regulation of MDM4 (MDMX) function by p76MDM2: a new facet in the control of p53 activity
Giglio, S., Mancini, F., Pellegrino, M., Conza, G. D., Puxeddu, E., Sacchi, A., Pontecorvi, A., & Moretti, F. (2010) · Oncogene · doi:10.1038/onc.2010.324 · Cited by 16 · see citing works
Sanford, J. D., Yang, J., Han, J., Tollini, L. A., Jin, A., & Zhang, Y. (2021) · BMC Molecular and Cell Biology · doi:10.1186/s12860-021-00385-3 · Cited by 7 · see citing works
In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway
Zhou, H., Wu, Z., Zhang, Y., Yu, Z., Nie, Z., Fan, J., Zhu, Z., Chen, F., & Wang, T. (2024) · Molecular Diversity · doi:10.1007/s11030-024-10833-9 · Cited by 6 · see citing works
FAM193A is a positive regulator of p53 activity
Szwarc, M. M., Guarnieri, A. L., Joshi, M. U., Duc, H. N., Laird, M. C., Pandey, A., Khanal, S., Dohm, E., Bui, A. K., Sullivan, K. D., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112230 · Cited by 6 · see citing works
Touqan, N. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University)
IN VIVO SIGNIFICANCE OF THE MDM4 AND P73 INTERACTION DURING DEVELOPMENT AND TUMORIGENESIS
Tashakori, M. (2015) · Digital Commons-TMC (Texas Medical Center)
Sanford, J. D., Yang, J., Han, J., Tollini, L. A., Jin, A., & Zhang, Y. (2021) · Figshare · doi:10.6084/m9.figshare.16664347
- Authors
- Ohtsubo, C., Shiokawa, D., Kodama, M., Gaiddon, C., Nakagama, H., Jochemsen, A. G., Taya, Y., & Okamoto, K.
- Affiliations
- Japan Science and Technology Agency (JP)
- National University of Singapore (SG)
- Inserm (FR)
- Leiden University Medical Center (NL)
- Corresponding author
- Taya, Yoichi
- Okamoto, Koji
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2009-06-10
- Volume
- 100
- Issue
- 7
- Pages
- 1291-1299
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC11159218
- OpenAlex
- W2041779012
- Cited by
- 32
- References
- 43
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 3 · 2020: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- Foundation for Promotion of Cancer Research
- 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 › Heat shock proteins research
- Keywords
- p53 inactivation, MDMX, MDM2, p53 ubiquitination, protein-protein interaction, neuroblastoma cells, tumor suppressor regulation
- MeSH terms
- Amino Acid Sequence, Cytoplasm, Humans, Molecular Sequence Data, Phosphorylation, Tumor Suppressor Protein p53, Cell Line, Tumor, Proto-Oncogene Proteins c-mdm2
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