The DOI matches its Crossref record; 46 of the 48 references it cites were found in a registry or an index.
ATM Phosphorylation of Mdm2 Ser394 Regulates the Amplitude and Duration of the DNA Damage Response in Mice
Open accessAbstract
DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in vivo, it does not appear to be a major regulator of p53 stability. We have utilized mice bearing altered Mdm2 alleles to demonstrate that ATM phosphorylation of Mdm2 serine 394 is required for robust p53 stabilization and activation after DNA damage. In addition, we demonstrate that dephosphorylation of Mdm2 Ser394 regulates attenuation of the p53-mediated response to DNA damage. Therefore, the phosphorylation status of Mdm2 Ser394 governs p53 protein levels and functions in cells undergoing DNA damage.
Overview
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
Verification
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?
In the citing paper
“By contrast, the mutation of Ser394 to alanine (Ser394Ala) in mouse MDM2 in vivo removes an ATM phosphorylation site, engenders radioresistance and increases the rate of spontaneous tumorigenesis to that observed in Trp53-hemizygous animals47.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
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
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2
Shieh, S.-Y., Ikeda, M., Taya, Y., & Prives, C. (1997) · Cell · doi:10.1016/s0092-8674(00)80416-x · Cited by 2,100
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051
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
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801
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 · cited 3×
“Mdm2 / mice die at E5–E6 during development due to aberrant p53-mediated apoptosis (Jones et al., 1995; Montes de Oca Luna et al., 1995), whereas Mdm2 overexpression in mice inhibits p53 tumor suppression, resulting in the formation of lymphomas, soft tissue sarcomas, and osteosarcomas (Jones et…”
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 · cited 3×
“Mdm2 / mice die at E5–E6 during development due to aberrant p53-mediated apoptosis (Jones et al., 1995; Montes de Oca Luna et al., 1995), whereas Mdm2 overexpression in mice inhibits p53 tumor suppression, resulting in the formation of lymphomas, soft tissue sarcomas, and osteosarcomas (Jones et al.”
Self-citationHickson, I., Zhao, Y., Richardson, C. J., Green, S. J., Martin, N. M. B., Orr, A. I., Reaper, P. M., Jackson, S. P., Curtin, N. J., & Smith, G. C. M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2727 · Cited by 1,220
Puma is an essential mediator of p53-dependent and -independent apoptotic pathways
Jeffers, J. R., Parganas, E., Lee, Y., Yang, C., Wang, J., Brennan, J. A., Maclean, K. H., Han, J., Chittenden, T., Ihle, J. N., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00244-7 · Cited by 880
ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
Maya, R., Balass, M., Kim, S.-T., Shkedy, D., Leal, J.-F. M., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., et al. (2001) · Genes & Development · doi:10.1101/gad.886901 · Cited by 731
Assessing TP53 status in human tumours to evaluate clinical outcome
Soussi, T., & Béroud, C. (2001) · Nature reviews. Cancer · doi:10.1038/35106009 · Cited by 659
The role of p53 in determining sensitivity to radiotherapy
Gudkov, A. V., & Komarova, E. A. (2003) · Nature reviews. Cancer · doi:10.1038/nrc992 · Cited by 581
Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice.
Harvey, M., McArthur, M. J., Montgomery, C. A., Butel, J. S., Bradley, A., & Donehower, L. A. (1993) · Nature Genetics · doi:10.1038/ng1193-225 · Cited by 542
Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage
Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y., & Shkedy, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14973 · Cited by 461
O’Gorman, S., Dagenais, N., Qian, M., & Marchuk, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14602 · Cited by 436
PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints
Lu, X., Nannenga, B., & Donehower, L. A. (2005) · Genes & Development · doi:10.1101/gad.1291305 · Cited by 389
Accelerated MDM2 auto‐degradation induced by DNA‐damage kinases is required for p53 activation
Stommel, J. M., & Wahl, G. M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600145 · Cited by 386 · cited 1×
“Mdm2 destabilization in response to DNA damage has been shown previously (Stommel and Wahl, 2004), and we observed an initial decrease in Mdm2 protein in both WT and A/A tissues.”
Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis
Jones, S. N., Hancock, A. R., Vogel, H., Donehower, L. A., & Bradley, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15608 · Cited by 386
Self-citationp53-deficient mice are extremely susceptible to radiation-induced tumorigenesis
Kemp, C. J., Wheldon, T. E., & Balmain, A. (1994) · Nature Genetics · doi:10.1038/ng0994-66 · Cited by 370
Wip1 Phosphatase Modulates ATM-Dependent Signaling Pathways
Shreeram, S., Demidov, O. N., Hee, W. K., Yamaguchi, H., Onishi, N., Kek, C., Timofeev, O. N., Dudgeon, C., Fornace, A. J., Anderson, C. W., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.07.010 · Cited by 358
Juven‐Gershon, T., Barak, Y., Zauberman, A., George, D. L., & Oren, M. (1993) · PubMed · Cited by 332
MDM2 is a Central Node in the p53 Pathway: 12 Years and Counting
Bond, G. L., Hu, W., & Levine, A. J. (2005) · Current Cancer Drug Targets · doi:10.2174/1568009053332627 · Cited by 310
The Wip1 Phosphatase Acts as a Gatekeeper in the p53-Mdm2 Autoregulatory Loop
Lu, X., Ma, O., Nguyen, T., Jones, S. N., Oren, M., & Donehower, L. A. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.08.033 · Cited by 290
Self-citationThe p53 family: guardians of maternal reproduction
Levine, A. J., Tomasini, R., McKeon, F., Mak, T. W., & Melino, G. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3086 · Cited by 260
Lu, X., Nguyen, T., Moon, S.-H., Darlington, Y. F., Sommer, M., & Donehower, L. A. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9127-x · Cited by 251
Komarova, E. A., Kondratov, R. V., Wang, K., Christov, K. T., Golovkina, T. V., Goldblum, J. R., & Gudkov, A. V. (2004) · Oncogene · doi:10.1038/sj.onc.1207494 · Cited by 235
Regulation of Transcription Functions of the p53 Tumor Suppressor by the mdm-2 Oncogene
Chen, J., Lin, J., & Levine, A. J. (1995) · Molecular Medicine · doi:10.1007/bf03401562 · Cited by 214
Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo
Pellegrini, M., Celeste, A., Difilippantonio, S., Guo, R., Wang, W., Feigenbaum, L., & Nussenzweig, A. (2006) · Nature · doi:10.1038/nature05112 · Cited by 209
Gajjar, M. K., Candeias, M. M., Malbert-Colas, L., Mazars, A., Fujita, J., Olivares‐Illana, V., & Fåhræus, R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.11.016 · Cited by 177
Phosphorylation of murine p53 at Ser-18 regulates the p53 responses to DNA damage
Chao, C., Saito, S., Anderson, C. W., Appella, E., & Xu, Y. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220252297 · Cited by 168
ATM activates p53 by regulating MDM2 oligomerization and E3 processivity
Cheng, Q., Chen, L., Li, Z., Lane, W. S., & Chen, J. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.294 · Cited by 165
Ser18 and 23 phosphorylation is required for p53‐dependent apoptosis and tumor suppression
Chao, C., Herr, D., Chun, J., & Xu, Y. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601167 · Cited by 158
Phosphorylation of Serine 18 Regulates Distinct p53 Functions in Mice
Sluss, H. K., Armata, H., Gallant, J., & Jones, S. N. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.3.976-984.2004 · Cited by 152
Self-citationCell Type- and Promoter-specific Roles of Ser18 Phosphorylation in Regulating p53 Responses
Chao, C., Hergenhahn, M., Kaeser, M. D., Wu, Z., Saito, S., Iggo, R., Hollstein, M., Appella, E., & Xu, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306938200 · Cited by 141
Jack, M. T., Woo, R. A., Hirao, A., Cheung, A., Mak, T. W., & Lee, P. W. K. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152053599 · Cited by 140
Mutation of Mouse p53 Ser23 and the Response to DNA Damage
Wu, Z., Earle, J., Saito, S., Anderson, C. W., Appella, E., & Xu, Y. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.8.2441-2449.2002 · Cited by 103
Wang, Y. V., Leblanc, M., Wade, M., Jochemsen, A. G., & Wahl, G. M. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.008 · Cited by 79
Regulation of MDM2 E3 Ligase Activity by Phosphorylation after DNA Damage
Cheng, Q., Cross, B. L., Li, B., Chen, L., Li, Z., & Chen, J. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05553-11 · Cited by 78
Gurley, K. E., & Kemp, C. J. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-07-0223 · Cited by 21
Phosphorylation of p53 Serine 18 Upregulates Apoptosis to Suppress Myc-Induced Tumorigenesis
Sluss, H. K., Gannon, H., Coles, A. H., Shen, Q., Eischen, C. M., & Jones, S. N. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0324 · Cited by 16
Self-citationGeneration of an Mdm2 conditional allele in mice
Steinman, H. A., & Jones, S. N. (2002) · genesis · doi:10.1002/gene.10035 · Cited by 14
Self-citation
Flagged first, then by citations
2 of the 48 references couldn’t be matched to a known paper.
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
Drugging the p53 pathway: understanding the route to clinical efficacy
Khoo, K. H., Verma, C. S., & Lane, D. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4236 · Cited by 742
Regulation of the p53 response and its relationship to cancer
Meek, D. W. (2015) · Biochemical Journal · doi:10.1042/bj20150517 · Cited by 311
Chibaya, L., Karim, B. O., Zhang, H., & Jones, S. N. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003193118 · Cited by 191
Self-citationThe ATM signaling network in development and disease
Stracker, T. H., Roig, I., Knobel, P. A., & Marjanović, M. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00037 · Cited by 192
Metadata
- Authors
- Gannon, H. S., Woda, B. A., & Jones, S. N.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Jones, Stephen N.
- ORCID
- Gannon, Hugh S.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 21
- Issue
- 5
- Pages
- 668-679
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3360886
- OpenAlex
- W2117932700
- Cited by
- 105
- References
- 48
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 10 · 2017: 5 · 2016: 13 · 2015: 4 · 2014: 11 · 2013: 10 · 2012: 6
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 442 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (CA077735)
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- ATM kinase, MDM2, p53 stabilization, DNA damage response, ionizing radiation, p53 activation
- MeSH terms
- Animals, DNA Damage, DNA-Binding Proteins, Enzyme Activation, Intestine, Small, Mice, Inbred C57BL, Phosphorylation, Radiation Tolerance, Serine, Spleen, Thymus Gland, Time Factors, Tumor Suppressor Protein p53, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Mutation, Missense, Tumor Suppressor Proteins, Mice, Proto-Oncogene Proteins c-mdm2, Protein Stability, Mice, 129 Strain, Ataxia Telangiectasia Mutated Proteins
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
