Cited by 122Cancer-related Molecular Pathways14-3-3 protein interactionsDNA Repair Mechanisms

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Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3

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LeBron, Cynthia, Chen, Lihong, Gilkes, Daniele M, Chen, Jiandong·2006·The EMBO Journal

DOI 10.1038/sj.emboj.7601032PMC PMC1422166

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Abstract

The MDM2 homolog MDMX is an important regulator of p53 during mouse embryonic development. DNA damage promotes MDMX phosphorylation, nuclear translocation, and degradation by MDM2. Here we show that MDMX copurifies with 14-3-3, and DNA damage stimulates MDMX binding to 14-3-3. Chk2-mediated phosphorylation of MDMX on S367 is important for stimulating 14-3-3 binding, MDMX nuclear import by a cryptic nuclear import signal, and degradation by MDM2. Mutation of MDMX S367 inhibits ubiquitination and degradation by MDM2, and prevents MDMX nuclear import. Expression of 14-3-3 stimulates the degradation of phosphorylated MDMX. Chk2 and 14-3-3 cooperatively stimulate MDMX ubiquitination and overcome the inhibition of p53 by MDMX. These results suggest that MDMX-14-3-3 interaction plays a role in p53 response to DNA damage by regulating MDMX localization and stability.

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Items 201–253 of 253

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O'Neill, T. B., Giarratani, L., Chen, P., Iyer, L. K., Lee, C. H., Bobiak, M., Kanai, F., Zhou, B. S., Chung, J. H., & Rathbun, G. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111705200 · Cited by 139
Inactivation of p53 but Not p73 by Adenovirus Type 5 E1B 55-Kilodalton and E4 34-Kilodalton Oncoproteins
Roth, J. C., König, C., Wienzek‐Lischka, S., Weigel, S., Ristea, S., & Dobbelstein, M. (1998) · Journal of Virology · doi:10.1128/jvi.72.11.8510-8516.1998 · Cited by 134
A new type of p16INK4/MTS1 gene transcript expressed in B-cell malignancies.
Duro, D., Bernard, O., Della-Valle, V., Berger, R., & Larsen, C. (1995) · PubMed · Cited by 130
DNA Damage-Induced Phosphorylation of MdmX at Serine 367 Activates p53 by Targeting MdmX for Mdm2-Dependent Degradation
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
Expression and Structural Analysis of 14-3-3 Proteins
Jones, D. H., Martin, H., Madrazo, J., Robinson, K., Nielsen, P., Roseboom, P. H., Patel, Y., Howell, S. A., & Aitken, A. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.0031 · Cited by 128
Regulation of the MDM2-p53 Pathway by Ribosomal Protein L11 Involves a Post-ubiquitination Mechanism
Dai, M., Shi, D., Jin, Y., Sun, X., Zhang, Y., Grossman, S. R., & Lu, H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602596200 · Cited by 124
Regulation of Molecular Chaperone Gene Transcription Involves the Serine Phosphorylation, 14-3-3ε Binding, and Cytoplasmic Sequestration of Heat Shock Factor 1
Wang, X., Grammatikakis, N., Siganou, A., & Calderwood, S. K. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6013-6026.2003 · Cited by 123
14-3-3 proteins: biological function and domain structure
Aitken, A., Jones, D., Soneji, Y., & Howell, S. A. (1995) · Biochemical Society Transactions · doi:10.1042/bst0230605 · Cited by 122
Synergy between the Mos/Mitogen-Activated Protein Kinase Pathway and Loss of p53 Function in Transformation and Chromosome Instability
Fukasawa, K., & Woude, G. F. V. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.1.506 · Cited by 117
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 116
A Novel MDMX Transcript Expressed in a Variety of Transformed Cell Lines Encodes a Truncated Protein with Potent p53 Repressive Activity
Rallapalli, R., Strachan, G. D., Cho, B., Mercer, W. E., & Hall, D. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.8299 · Cited by 113
Cdc25B activity is regulated by 14-3-3
Forrest, A. R. R., & Gabrielli, B. G. (2001) · Oncogene · doi:10.1038/sj.onc.1204574 · Cited by 112
Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor
McGowan, C. H. (2002) · BioEssays · doi:10.1002/bies.10101 · Cited by 109
SUMO-1 and p53
Melchior, F., & Hengst, L. (2002) · Cell Cycle · doi:10.4161/cc.1.4.131 · Cited by 109
Differentiation of Hdm2-mediated p53 ubiquitination and Hdm2 autoubiquitination activity by small molecular weight inhibitors
Lai, Z., Yang, T., Kim, Y. B., Sielecki, T. M., Diamond, M. A., Strack, P. R., Rolfe, M., Caligiuri, M., Benfield, P. A., Auger, K. R., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212428599 · Cited by 106
Targets of oncogenes and tumor suppressors: key for understanding basic mechanisms of carcinogenesis.
Kopnin, B. P. (2000) · PubMed · Cited by 95
MDM2 and MDMX can interact differently with ARF and members of the p53 family
Wang, X., Arooz, T., Siu, W. Y., Chiu, C. H. S., Lau, A., Yamashita, K., & Poon, R. Y. C. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02124-x · Cited by 94
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
A Genetic Approach to Mapping the p53 Binding Site in the MDM2 Protein
Freedman, D. A., Epstein, C. B., Roth, J. C., & Levine, A. J. (1997) · Molecular Medicine · doi:10.1007/bf03401678 · Cited by 91
A Role for 14-3-3τ in E2F1 Stabilization and DNA Damage-induced Apoptosis
Wang, B., Liu, K., Lin, F., & Lin, W.-C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410493200 · Cited by 91
The p53-associated protein MDM2 contains a newly characterized zinc-binding domain called the RING finger
Boddy, M. N., Freemont, P. S., & Borden, K. L. B. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90020-5 · Cited by 91
Caged phosphopeptides reveal a temporal role for 14-3-3 in G1 arrest and S-phase checkpoint function
Nguyen, A., Rothman, D. M., Stehn, J. R., Imperiali, B., & Yaffe, M. B. (2004) · Nature Biotechnology · doi:10.1038/nbt997 · Cited by 91
A New Twist in the Feedback Loop: Stress-Activated MDM2 Destabilization is Required for p53 Activation
Stommel, J. M., & Wahl, G. M. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1522 · Cited by 90
Hdmx Recruitment into the Nucleus by Hdm2 Is Essential for Its Ability to Regulate p53 Stability and Transactivation
Migliorini, D., Danovi, D., Colombo, E., Carbone, R., Pelicci, P. G., & Marine, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108795200 · Cited by 88
Regulation of p53-MDMX interaction by casein kinase 1 alpha
Chen, L., Li, C., Pan, Y., & Chen, J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6509-6520.2005 · Cited by 88
Self-citation
DNA Damage Induces MDMX Nuclear Translocation by p53-Dependent and -Independent Mechanisms
Li, C., Chen, L., & Chen, J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.21.7562-7571.2002 · Cited by 82
Binding of p53 to the Central Domain of Mdm2 Is Regulated by Phosphorylation
Kulikov, R., Winter, M., & Blattner, C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513311200 · Cited by 79
MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation
Jackson, M. W., Lindström, M. S., & Berberich, S. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010685200 · Cited by 74
Switching mechanisms of cell death in mdm2- and mdm4-null mice by deletion of p53 downstream targets.
Chávez‐Reyes, A., Parant, J. M., Amelse, L. L., Luna, R. M. D. O., Korsmeyer, S. J., & Lozano, G. (2003) · PubMed · Cited by 73
Mdm2, but not Mdm4, protects terminally differentiated smooth muscle cells from p53-mediated caspase-3-independent cell death
Boesten, L. S. M., Zadelaar, S. M., De Clercq, S., Francoz, S., van Nieuwkoop, A., Biessen, E. A. L., Hofmann, F., Feil, S., Feil, R., Jochemsen, A. G., et al. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401973 · Cited by 70
p14(ARF) modulates the cytolytic effect of ONYX-015 in mesothelioma cells with wild-type p53.
Yang, C., You, L., Uematsu, K., Yeh, C., McCormick, F. P., & Jablons, D. M. (2001) · PubMed · Cited by 69
14-3-3 Family Members Act Coordinately to Regulate Mitotic Progression
Dalal, S. N., Yaffe, M. B., & DeCaprio, J. A. (2004) · Cell Cycle · doi:10.4161/cc.3.5.856 · Cited by 68
Stabilization of the MDM2 Oncoprotein by Mutant p53
Peng, Y., Chen, L., Li, C., Lu, W., Agrawal, S., & Chen, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c000781200 · Cited by 67
Cell cycle roles for two 14-3-3 proteins duringDrosophiladevelopment
Su, T. T., Parry, D. H., Donahoe, B., Chien, C., O’Farrell, P. H., & Purdy, A. K. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.19.3445 · Cited by 60
Substitutions that compromise the ionizing radiation-induced association of p53 with 14-3-3 proteins also compromise the ability of p53 to induce cell cycle arrest.
Stavridi, E. S., Chehab, N. H., Malikzay, A., & Halazonetis, T. D. (2001) · PubMed · Cited by 54
Rescue of Mdm4-deficient mice by Mdm2 reveals functional overlap of Mdm2 and Mdm4 in development
Steinman, H. A., Hoover, K. L., Keeler, M. L., Sands, A., & Jones, S. N. (2005) · Oncogene · doi:10.1038/sj.onc.1208930 · Cited by 52
Dose-dependent effects of DNA-damaging agents on p53-mediated cell cycle arrest.
Chang, D., Chen, F., Zhang, F., McKay, B. C., & Ljungman, M. E. (1999) · PubMed · Cited by 48
ATM: Ready, Set, Go
Shiloh, Y. (2003) · Cell Cycle · doi:10.4161/cc.2.2.342 · Cited by 45
Neddylating the Guardian
Harper, J. W. (2004) · Cell · doi:10.1016/j.cell.2004.06.015 · Cited by 45
PRIMA-1 induces apoptosis by inhibiting JNK signaling but promoting the activation of Bax
Wang, T., Lee, K., Rehman, A., & Daoud, S. S. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.11.006 · Cited by 41
Control of p53 nuclear accumulation in stressed cells
Inoue, T. M., Wu, L., Stuart, J., & Maki, C. G. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.006 · Cited by 40
Protein synthesis—dependent cytoplasmic translocation of p53 protein after serum stimulation of growth‐arrested MCF‐7 cells
Takahashi, K., Sumimoto, H., Suzuki, K., & Ono, T. (1993) · Molecular Carcinogenesis · doi:10.1002/mc.2940080112 · Cited by 39
Nuclear Trafficking
Stewart, M. (2003) · Science · doi:10.1126/science.1092863 · Cited by 31
Regulation of transcription by E2F1/DP1
Martin, K., Trouche, D., Hagemeier, C., & Kouzarides, T. (1995) · Journal of Cell Science · doi:10.1242/jcs.1995.supplement_19.13 · Cited by 30
14‐3‐3 proteins integrate E2F activity with the DNA damage response
Milton, A. H., Khaire, N., Ingram, L., O'donnell, A. J., & Thangue, N. B. L. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600999 · Cited by 29
Nuclear pore complexes: dynamics in unexpected places
Lyman, S. K., & Gerace, L. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200106071 · Cited by 27
Constitutive mdmx Expression During Cell Growth, Differentiation, and DNA Damage
Jackson, M. W., & Berberich, S. J. (1999) · DNA and Cell Biology · doi:10.1089/104454999314971 · Cited by 27
Exogenous wt-p53 protein is active in transformed cells but not in their non-transformed counterparts: implications for cancer gene therapy without tumor targeting
D’Orazi, G., Marchetti, A., Crescenzi, M., Coen, S., Sacchi, A., & Soddu, S. (2000) · The Journal of Gene Medicine · doi:10.1002/(sici)1521-2254(200001/02)2:1 · Cited by 26
Role of the 14–3–3 protein in carbon metabolism of the pathogenic yeast Candida albicans
Wang, Y. K., Das, B., Huber, D. H., Wellington, M. A., Kabir, M. A., Sherman, F., & Rustchenko, E. P. (2004) · Yeast · doi:10.1002/yea.1079 · Cited by 25
Determination of amino acid pairs in human p53 protein sensitive to mutations/variants by means of a random approach
Wu, G. M., & Yan, S. (2003) · Journal of Molecular Modeling · doi:10.1007/s00894-003-0155-8 · Cited by 19
Column chromatography and spectroscopy in the analysis of airborne polycyclics
Zdrojewski, Z., Dubois, L., Moore, G. E., Thomas, R. S., & Monkman, J. L. (1967) · Journal of Chromatography A · doi:10.1016/s0021-9673(01)85972-0 · Cited by 14
Gene replacement strategies for cancer.
Roth, J. A. (1996) · PubMed · Cited by 7
Cellular senescence and cancer
(1999) · doi:10.1002/(sici)1096-9896(199901)187:1

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Zannini, L., Delia, D., & Buscemi, G. (2014) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mju045 · Cited by 455
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Wade, M., Wang, Y. V., & Wahl, G. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.009 · Cited by 450
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Pennington, K. L., Ty, C., Torres, M. P., & Andersen, J. (2018) · Oncogene · doi:10.1038/s41388-018-0348-3 · Cited by 383
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Authors: LeBron, C., Chen, L., Gilkes, D. M., & Chen, J.
Affiliations: Moffitt Cancer Center (US)
Corresponding author: Chen, Jiandong
ORCID: Chen, Lihong
Gilkes, Daniele M
Chen, Jiandong
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2006-03-02
Volume: 25
Issue: 6
Pages: 1196-1206
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/sj.emboj.7601032
PMC: PMC1422166
OpenAlex: W2068624303
Cited by: 122
References: 255
Citations by year: 2025: 2 · 2024: 3 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 2 · 2014: 7 · 2013: 11 · 2012: 9
FWCI: 6.78
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
Funders: American Cancer Society
National Institutes of Health
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: MDMX, Chk2, MDM2, p53, DNA damage response, nuclear import, protein degradation, ubiquitination, phosphorylation, nuclear import signal, protein stability, mouse embryo development
MeSH terms: Animals, Breast Neoplasms, DNA Damage, Gene Expression Regulation, HeLa Cells, Humans, Nuclear Proteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Osteosarcoma, Tumor Suppressor Protein p53, Mice, Knockout, Cell Cycle Proteins, Active Transport, Cell Nucleus, Ubiquitin, Immunoprecipitation, 14-3-3 Proteins, Cyclin-Dependent Kinase 2, Mice

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Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3

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