Cited by 92Cancer-related Molecular PathwaysAdvanced Proteomics Techniques and ApplicationsGenomics and Chromatin Dynamics

Identification and Characterization of a Novel p300-mediated p53 Acetylation Site, Lysine 305

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Wang, Yan-Hsiung, Tsay, Yeou-Guang, Tan, Bertrand Chin-Ming, Lo, Wen-Yi, Lee, Sheng-Chung·2003·Journal of Biological Chemistry

Abstract

Post-translational modifications serve as important regulatory elements in modulating the transcriptional activity of the tumor suppressor protein p53. We have previously reported a tandem mass spectrometry-based method (viz. selected ion tracing analysis) that can be applied to the identification of phosphopeptides as well as exact mapping of the phosphorylated residues within. In this study, we describe the application of the same strategy for the identification of p300 acetyltransferase-mediated acetylation sites on p53. Consistent with the previous finding, lysines 370, 372, 373, 381, and 382 were detected by this modified selected ion tracing method as the target sites of p300 in vitro. Moreover, two novel acetylation sites, Lys-292 and Lys-305, were also found. Immunoblotting using anti-acetyl-Lys-305 antibody confirmed this discovery and demonstrated that Lys-305 could be acetylated by p300 both in vitro and in vivo. We also show that an alanine or glutamine substitution at Lys-305 (K305A or K305Q) suppressed the transcriptional activity of p53, whereas an arginine mutation (K305R) increased the transcriptional activity. Thus, p300 may further regulate the transcriptional activity of p53 through a novel acetylation site, Lys-305.

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Authors
Wang, Y.-H., Tsay, Y.-G., Tan, B. C.-M., Lo, W.-Y., & Lee, S.-C.
Affiliations
National Taiwan University (TW)
Corresponding author
Lee, Sheng-Chung
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-07
Volume
278
Issue
28
Pages
25568-25576
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2081774189
Cited by
92
References
37
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 4
FWCI
2.69
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Council
  • Academia Sinica
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
p53, P300, lysine acetylation, acetylation sites, post-translational modification, transcriptional activity, tumor suppressor regulation, site-directed mutagenesis
MeSH terms
p300-CBP-Associated Factor, Acetyltransferases, Alanine, Amino Acid Sequence, Butyrates, DNA, Glutamine, Humans, Ions, Lysine, Molecular Sequence Data, Peptides, Plasmids, Protein Binding, Mass Spectrometry, Time Factors, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Ultraviolet Rays, Immunoblotting, Blotting, Western, Tumor Suppressor Protein p53, Mutagenesis, Site-Directed, Genes, Reporter, Cell Cycle Proteins, p300-CBP Transcription Factors, Histone Acetyltransferases, Isobutyrates

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