The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Crosstalk between sumoylation and acetylation regulates p53-dependent chromatin transcription and DNA binding
Open accessAbstract
Covalent modification by small ubiquitin-related modifiers (SUMO) regulates p53 transcription activity through an undefined mechanism. Using reconstituted sumoylation components, we purified SUMO-1-conjugated p53 (Su-p53) to near homogeneity. Su-p53 exists in solution as a tetramer and interacts with p300 histone acetyltransferase as efficiently as the unmodified protein. Nevertheless, it fails to activate p53-dependent chromatin transcription because of its inability to bind DNA. With sequential modification assays, we found that sumoylation of p53 at K386 blocks subsequent acetylation by p300, whereas p300-acetylated p53 remains permissive for ensuing sumoylation at K386 and alleviates sumoylation-inhibited DNA binding. While preventing the free form of p53 from accessing its cognate sites, sumoylation fails to disengage prebound p53 from DNA. The sumoylation-deficient K386R protein, when expressed in p53-null cells, exhibits higher transcription activity and binds better to the endogenous p21 gene compared with the wild-type protein. These studies unravel a molecular mechanism underlying sumoylation-regulated p53 function and further uncover a new role of acetylation in antagonizing the inhibitory effect of sumoylation on p53 binding to DNA.
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“Competition between Mdm2 and other proteins for modification of these sites may therefore contribute to p53 function [127].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [127]
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Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
Gu, W., & Roeder, R. G. (1997) · Cell · doi:10.1016/s0092-8674(00)80521-8 · Cited by 2,559
RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO
Hoege, C., Pfander, B., Moldovan, G., Pyrowolakis, G., & Jentsch, S. (2002) · Nature · doi:10.1038/nature00991 · Cited by 2,202
Transcriptional control of human p53-regulated genes
Riley, T., Sontag, E., Chen, P., & Levine, A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2395 · Cited by 1,921
Johnson, E. S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.074118 · Cited by 1,711
A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ
Pascual, G., Fong, A. L., Ogawa, S., Gamliel, A., Li, A. C., Perissi, V., Rose, D. W., Willson, T. M., Rosenfeld, M. G., & Glass, C. K. (2005) · Nature · doi:10.1038/nature03988 · Cited by 1,287
Matunis, M. J., Coutavas, E. E., & Blobel, G. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.135.6.1457 · Cited by 1,199
Post‐translational modifications and activation of p53 by genotoxic stresses
Appella, E., & Anderson, C. W. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02225.x · Cited by 1,095
Lysine Acetylation: Codified Crosstalk with Other Posttranslational Modifications
Yang, X.-J., & Seto, E. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.07.002 · Cited by 1,006
The General Transcription Machinery and General Cofactors
Thomas, M. C., & Chiang, C. (2006) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230600648736 · Cited by 992
Functional Heterogeneity of Small Ubiquitin-related Protein Modifiers SUMO-1 versus SUMO-2/3
Saitoh, H., & Hinchey, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.9.6252 · Cited by 897
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Sumoylation: A Regulatory Protein Modification in Health and Disease
Flotho, A., & Melchior, F. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061909-093311 · Cited by 1,124
Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting
Borrero, L. J. H., & El‐Deiry, W. S. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188556 · Cited by 805
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
SUMO and the robustness of cancer
Seeler, J.-S., & Dejean, A. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.143 · Cited by 443
p53 modifications: exquisite decorations of the powerful guardian
Liu, Y., Tavana, O., & Gu, W. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz060 · Cited by 392
Metadata
- Authors
- Wu, S., & Chiang, C.
- Affiliations
- Harold C. Simmons Comprehensive Cancer Center (US)
- Corresponding author
- Chiang, Cheng‐Ming
- Venue
- The EMBO Journal
- Published
- 2009-04-02
- Volume
- 28
- Issue
- 9
- Pages
- 1246-1259
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC2683057
- OpenAlex
- W2073590048
- Cited by
- 125
- References
- 68
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 1 · 2022: 8 · 2021: 12 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 12 · 2012: 12
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA103867, R01CA103867, R01CA124760, CA124760)
- 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 › Genomics and Chromatin Dynamics
- Keywords
- p53, SUMOylation, acetylation, SUMO1, P300, histone acetyltransferase, p53 DNA binding, chromatin transcription, post-translational modification, p21 gene, p53 tetramer, transcriptional activation
- MeSH terms
- p300-CBP-Associated Factor, Acetylation, Chromatin, Chromatography, Gel, DNA, Humans, Protein Binding, Transcription, Genetic, Tumor Suppressor Protein p53, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, Small Ubiquitin-Related Modifier Proteins, Cell Line, Tumor, Chromatin Immunoprecipitation, p300-CBP Transcription Factors
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