Regulation of histone deacetylase 2 by protein kinase CK2
Open accessAbstract
Histone deacetylase 2 (HDAC2) is a member of a large family of enzymes that alter gene expression by catalyzing the removal of acetyl groups from core histones. Originally isolated as a transcriptional co-repressor, HDAC2 possesses extensive amino acid sequence homology to HDAC1 (the founding member and most extensively studied HDAC enzyme). Because of this high degree of sequence similarity between HDAC1 and HDAC2, coupled with the fact that the two always co-exist in the same complexes, it is difficult to assess whether different properties exist between these two proteins. We report here that HDAC2 is a phosphoprotein similar to HDAC1. In addition, like HDAC1, the phospho-acceptor sites in HDAC2 are located in the C-terminal portion of the protein. However, unlike HDAC1, which can be phosphorylated by protein kinase CK2, cAMP-dependent protein kinase, and protein kinase G, HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. Together, our data indicate that like many HDACs, HDAC2 is regulated by post-translational modification, particularly phosphorylation. Furthermore, we demonstrate for the first time that there are similarities and differences in the regulation of HDAC1 and HDAC2 by phosphorylation.
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The activities of class I HDACs are regulated by posttranslational modifications to the C-terminal extension, such as sumoylation and phosphorylation, which may affect catalytic activities via an allosteric mechanism and/or by altering complex-forming capabilities.
“Additionally, the activities of class I HDACs are regulated by posttranslational modifications to the C-terminal extension, such as sumoylation (David et al., 2002) and phosphorylation (Tsai and Seto, 2002), which may affect their catalytic activities via an allosteric mechanism and/or by altering their complex forming capabilities.”
From Structural Snapshots of Human HDAC8 Provide Insights into the Class I Histone Deacetylases (2004) · cites this paper as Tsai and Seto, 2002
The paper’s introductory summary (page unavailable) reports C-terminal phosphorylation of HDAC2 and links it to enzymatic activity and complex formation. The discussion of HDAC2 interactions (page unavailable) suggests phosphorylation may alter its conformation. But the paper does not establish that these effects extend to class I HDACs generally: it reports phosphorylation of HDAC3 and HDAC8 only in vitro, without establishing its effects on their activity. The sentence cites David et al., not Tsai and Seto, for sumoylation. (LLM, conf=0.85)
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“Histone Deacetylation Assay For Figures 4J, 5C, and 5G, the HDAC6 full-length, HDAC6 dead mutant, and HDAC6 deletion proteins purified from Sf9 cells were assayed for their deacetylase activities as described in Tsai and Seto (2002).”
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- Authors
- Tsai, S.-C., & Seto, E.
- Affiliations
- University of South Florida (US)
- Corresponding author
- Seto, Edward
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 277
- Issue
- 35
- Pages
- 31826-31833
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2047809719
- Cited by
- 196
- References
- 6
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 5 · 2021: 10 · 2020: 11 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 8 · 2015: 4 · 2014: 9 · 2013: 16 · 2012: 9
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Moffitt Cancer Center
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM058486, GM58486)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- HDAC2, casein kinase 2, protein phosphorylation, HDAC1, post-translational modification, enzyme regulation, protein complex formation, transcriptional repression, protein kinase A, protein kinase G
- MeSH terms
- Amino Acid Sequence, Enzyme Repression, Flavonoids, HeLa Cells, Histone Deacetylases, Humans, Hydrolysis, Kinetics, Peptide Mapping, Phosphopeptides, Phosphoproteins, Phosphoserine, Repressor Proteins, Transcription, Genetic, Protein Serine-Threonine Kinases, Apigenin, Casein Kinase II, Histone Deacetylase 1, Histone Deacetylase 2
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