Histone deacetylase (HDAC) catalytic activity is regulated by formation of co-regulator complexes and post-translational modification. Whether these mechanisms are transformed in cancer and how this affects the binding and selectivity of HDAC inhibitors (HDACis) is unclear. In this study, we developed a method that identified a 3- to 16-fold increase in HDACi selectivity for HDAC3 in triple-negative breast cancer (TNBC) cells in comparison with luminal subtypes that was not predicted by current practice measurements with recombinant proteins. We found this increase was caused by c-Jun N-terminal kinase (JNK) phosphorylation of HDAC3, was independent of HDAC3 complex composition or subcellular localization, and was associated with a 5-fold increase in HDAC3 enzymatic activity. This study points to HDAC3 and the JNK axes as targets in TNBC, highlights how HDAC phosphorylation affects HDACi binding and selectivity, and outlines a method to identify changes in individual HDAC isoforms catalytic activity, applicable to any disease state.
Pubmed ID: 28943357 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets IgG
View all literature mentionsThis monoclonal targets HDAC3
View all literature mentionsThis monoclonal targets HDAC11
View all literature mentionsThis monoclonal targets HDAC10
View all literature mentionsThis monoclonal targets HDAC8
View all literature mentionsThis monoclonal targets p38 MAPK (D13E1) XP Rabbit mAb
View all literature mentionsThis monoclonal targets NF-κB p65
View all literature mentionsThis monoclonal targets JUN
View all literature mentionsThis polyclonal targets
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis monoclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets SAPK/JNK
View all literature mentionsThis monoclonal targets synthetic phosphopeptide corresponding to residues surrounding Thr183/Tyr185 of human SAPK/JNK
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis polyclonal targets TBL1 - ChIP Grade
View all literature mentionsThis monoclonal targets Akt1
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets Nuclear Receptor Corepressor NCoR - ChIP Grade
View all literature mentionsThis polyclonal targets NCOR2
View all literature mentionsThis polyclonal targets HDAC3, phospho (Ser424)
View all literature mentionsThis monoclonal targets HDAC3
View all literature mentionsThis monoclonal targets HDAC7
View all literature mentionsThis polyclonal targets HDAC6 antibody
View all literature mentionsThis monoclonal targets Hdac5
View all literature mentionsThis monoclonal targets HDAC4 (A-4)
View all literature mentionsThis unknown targets Widely expressed. Synthetic peptide: C-NEFYDGDHDNDKESDVEI conjugated to KLH, corresponding to amino acids 411-428 of Human HDAC3.
View all literature mentionsThis monoclonal targets HDAC2 antibody [EPR5001]
View all literature mentionsThis polyclonal targets HDAC1 - ChIP Grade
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line ZR-75-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets p38 MAPK, phospho (Thr180 / Tyr182)
View all literature mentionsThis polyclonal targets
View all literature mentionsThis polyclonal targets TBL1 - ChIP Grade
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis monoclonal targets Akt1
View all literature mentionsThis polyclonal targets Nuclear Receptor Corepressor NCoR - ChIP Grade
View all literature mentionsThis polyclonal targets HDAC3, phospho (Ser424)
View all literature mentionsThis monoclonal targets HDAC3
View all literature mentionsThis polyclonal targets HDAC1 - ChIP Grade
View all literature mentions