例如:"lncRNA", "apoptosis", "WRKY"

The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.

Oncogene. 2020 Mar;39(12):2583-2596. Epub 2020 Jan 27
Chinnadurai Mani 1 , Kaushlendra Tripathi 1 , Shan Luan 2 , David W Clark 1 , Joel F Andrews 1 , Alessandro Vindigni 3 , Gary Thomas 2 , Komaraiah Palle 4
Chinnadurai Mani 1 , Kaushlendra Tripathi 1 , Shan Luan 2 , David W Clark 1 , Joel F Andrews 1 , Alessandro Vindigni 3 , Gary Thomas 2 , Komaraiah Palle 4
+ et al

[No authors listed]

Author information
  • 1 Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, 36604, USA.
  • 2 University of Pittsburgh School of Medicine, 5117 Centre Avenue, Pittsburgh, PA, 15213, USA.
  • 3 Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, 63104, USA.
  • 4 Department of Surgery, Texas Tech University Health Sciences Centre, Lubbock, TX, 79430, USA. komaraiah.palle@ttuhsc.edu.

摘要


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.