The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability
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Phosphofurin acidic cluster sorting protein-1 (PACS-1) is a multifunctional membrane traffic regulator that plays important roles in organ homeostasis and disease. In this study, we elucidate a novel nuclear function for PACS-1 in maintaining chromosomal integrity. PACS-1 progressively accumulates in the nucleus during cell cycle progression, where it interacts with class I histone deacetylases 2 and 3 (HDAC2 and HDAC3) to regulate chromatin dynamics by maintaining the acetylation status of histones. PACS-1 knockdown results in the proteasome-mediated degradation of HDAC2 and HDAC3, compromised chromatin maturation, as indicated by elevated levels of histones H3K9 and H4K16 acetylation, and, consequently, increased replication stress-induced DNA damage and genomic instability.
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HDAC2, together with HDAC3, can form a noncanonical complex with PACS-1.
“HDAC2, together with HDAC3, can form a noncanonical complex with PACS-1 (phosphofurin acidic cluster sorting protein-1).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Mani et al., 2020
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References 53 · Cited by 27
- Authors
- Mani, C., Tripathi, K., Luan, S., Clark, D. W., Andrews, J. F., Vindigni, A., Thomas, G., & Palle, K.
- Affiliations
- Texas Tech University (US)
- USA Mitchell Cancer Institute (US)
- University of Pittsburgh (US)
- Saint Louis University (US)
- Corresponding author
- Palle, Komaraiah
- Venue
- Oncogene
- Published
- 2020-01-27
- Volume
- 39
- Issue
- 12
- Pages
- 2583-2596
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC7085454
- OpenAlex
- W3000986612
- Cited by
- 27
- References
- 53
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA219187)
- National Institute of General Medical Sciences (R01GM098956, R01GM108648)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK112844, R01DK114855)
- 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 › DNA Repair Mechanisms
- Keywords
- HDAC2, HDAC3, class I histone deacetylases, histone acetylation, genome stability, replication stress, DNA damage, proteasomal degradation, chromosome integrity
- MeSH terms
- Histone Deacetylase 3, Cell Cycle, Cell Nucleus, Chromatin, Cytosol, DNA Replication, HeLa Cells, Histone Deacetylases, Humans, Vesicular Transport Proteins, Genomic Instability, Cell Line, Tumor, Proteasome Endopeptidase Complex, Protein Stability, Gene Knockdown Techniques, Histone Deacetylase 1
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