Reference - Detail
|Author||Ishihara K, Kaneko M, Kitamura H, Takahashi A, Hong JJ, Seyama T, Iida K, Wada H, Hirasawa N, Ohuchi K.|
|Title||Mechanism for the decrease in the FIP1L1-PDGFRalpha protein level in EoL-1 cells by histone deacetylase inhibitors.|
|Journal||Int Arch Allergy Immunol|
BACKGROUND:Acetylation and deacetylation of proteins occur in cells in response to various stimuli, and are reversibly catalyzed by histone acetyltransferase and histone deacetylase (HDAC), respectively. EoL-1 cells have an FIP1L1-PDGFRA fusion gene that causes transformation of eosinophilic precursor cells into leukemia cells. The HDAC inhibitors apicidin and n-butyrate suppress the proliferation of EoL-1 cells and induce differentiation into eosinophils by a decrease in the protein level of FIP1L1-PDGFRalpha without affecting the mRNA level for FIP1L1-PDGFRA. In this study, we analyzed the mechanism by which the protein level of FIP1L1-PDGFRalpha is decreased by apicidin and n-butyrate.
METHODS:EoL-1 cells were incubated in the presence of the HDAC inhibitors apicidin, trichostatin A or n-butyrate. The protein levels of FIP1L1-PDGFRalpha and phosphorylated eIF-2alpha were determined by Western blotting. Actinomycin D and cycloheximide were used to block RNA synthesis and protein synthesis, respectively, in the chasing experiment of the amount of FIP1L1-PDGFRalpha protein.
RESULTS:When apicidin- and n-butyrate-treated EoL-1 cells were incubated in the presence of actinomycin D, the decrease in the protein level of FIP1L1-PDGFRalpha was significantly enhanced when compared with controls. In contrast, the protein levels were not changed by cycloheximide among these groups. Apicidin and n-butyrate induced the continuous phosphorylation of eIF-2alpha for up to 8 days.
CONCLUSIONS:The decrease in the level of FIP1L1-PDGFRalpha protein by continuous inhibition of HDAC may be due to the decrease in the translation rate of FIP1L1-PDGFRA.
|Volume||146 Suppl 1|
|MeSH||Acetylation / drug effects Blotting, Western Butyrates / pharmacology* Cell Differentiation / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cells, Cultured Enzyme Inhibitors / pharmacology* Eosinophils / drug effects* Eosinophils / metabolism Eukaryotic Initiation Factor-2 / analysis Eukaryotic Initiation Factor-2 / drug effects Eukaryotic Initiation Factor-2 / metabolism* Histone Deacetylase Inhibitors* Histone Deacetylases / metabolism Humans Hypereosinophilic Syndrome / drug therapy* Hypereosinophilic Syndrome / metabolism Oncogene Proteins, Fusion / analysis* Oncogene Proteins, Fusion / drug effects Oncogene Proteins, Fusion / metabolism Peptides, Cyclic / pharmacology* Receptor, Platelet-Derived Growth Factor alpha / analysis* Receptor, Platelet-Derived Growth Factor alpha / drug effects Receptor, Platelet-Derived Growth Factor alpha / metabolism mRNA Cleavage and Polyadenylation Factors / analysis* mRNA Cleavage and Polyadenylation Factors / drug effects mRNA Cleavage and Polyadenylation Factors / metabolism|
|WOS Category||ALLERGY IMMUNOLOGY|
|Human and Animal Cells|