Transforming Growth Factor-β Stimulates p300-dependent RUNX3 Acetylation, Which Inhibits Ubiquitination-mediated Degradation
Open accessAbstract
The Runt domain transcription factors (RUNXs) play essential roles in normal development and neoplasias. Genetic analyses of animals and humans have revealed the involvement of RUNX1 in hematopoiesis and leukemia, RUNX2 in osteogenesis and cleidocranial dysplasia, and RUNX3 in the development of T-cells and dorsal root ganglion neurons and in the genesis of gastric cancer. Here we report that RUNX3 is a target of the acetyltransferase activity of p300. The p300-dependent acetylation of three lysine residues protects RUNX3 from ubiquitin ligase Smurf-mediated degradation. The extent of the acetylation is up-regulated by the transforming growth factor-beta signaling pathway and down-regulated by histone deacetylase activities. Our findings demonstrate that the level of RUNX3 protein is controlled by the competitive acetylation and deacetylation of the three lysine residues, revealing a new mechanism for the posttranslational regulation of RUNX3 expression.
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HDAC3, and not HDAC4, -5, -7, or the HDAC3 Y298F mutant, is able to efficiently deacetylate two of the three Runx3 K residues (K148 and K186) previously shown to be acetylated.
“During the screening of a library of acetylated peptides representative of the known ''acetylome,'' we have indeed observed (P.G., A.L., C.P., and C.S., unpublished data) that HDAC3, and not HDAC4, -5, -7, or the HDAC3 Y298F mutant, is able to efficiently deacetylate two of the three Runx3 K residues (K148 and K186) previously shown to be acetylated (27).”
From Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases (2007) · cites this paper as [27]
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References 38 · Cited by 211
Research works printed but not linked: 3
- Woolf, E., Xiao, C., Fainaru, O., Lotem, J., Rosen, D., Negreanu, V., Bernstein, Y., Goldenberg, D., Brenner, O., Berke, G., Levanon, D., and Groner, Y. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 7731-7736
- Levanon, D., Goldstein, R. E., Bernstein, Y., Tang, H., Goldenberg, D., Stifani, S., Paroush, Z., and Groner, Y. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 11590 -11595
- Ogawa, E., Maruyama, M., Kagoshima, H., Inuzuka, M., Lu, J., Satake, M., Shigesada, K., and Ito, Y. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6859 -6863
- Authors
- Jin, Y.-H., Jeon, E.-J., Li, Q.-L., Lee, Y. H., Choi, J.-K., Kim, W.-J., Lee, K.-Y., & Bae, S.-C.
- Affiliations
- Chungbuk National University (KR)
- Corresponding author
- Lee, Kwang-Youl
- Bae, Suk-Chul
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 279
- Issue
- 28
- Pages
- 29409-29417
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1981301540
- Cited by
- 211
- References
- 38
- Citations by year
- 2025: 7 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 10 · 2019: 10 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 11 · 2014: 15 · 2013: 9 · 2012: 17
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- RUNX3, P300, histone acetylation, lysine acetylation, TGF-beta signaling, histone deacetylase, post-translational regulation, protein stability
- MeSH terms
- p300-CBP-Associated Factor, Acetylation, Acetyltransferases, Animals, Cell Line, DNA-Binding Proteins, Humans, Hydroxamic Acids, Lysine, Protein Processing, Post-Translational, Protein Synthesis Inhibitors, Recombinant Fusion Proteins, Transcription Factors, Signal Transduction, Transcriptional Activation, Transforming Growth Factor beta, Genes, Reporter, Cell Cycle Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Core Binding Factor Alpha 3 Subunit, p300-CBP Transcription Factors, Histone Acetyltransferases
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