Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells.
We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA) effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the signal transduction pathway from T cell receptor to nucleus. Using reverse transcription real-time quantitative PCR and Western blotting analysis we observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down-regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9 and 1.7 h, respectively. Employing the protein biosynthesis inhibitor cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP-70, LAT and SLP-76 content in T cells confirms an immunosuppressive effect by TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of autoimmune diseases.
Januchowski
Radosław
R
Karol Marcinkowski University of Medical Sciences, Department of Biochemistry and Molecular Biology, Poznań, Poland.
Jagodzinski
Paweł P
PP
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007166:Immunosuppressive Agents; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C092947:SLP-76 signal Transducing adaptor proteins; C012589:trichostatin A; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human