Nuclear factor of activated T cells (NFAT) is a possible target for dexamethasone in thymocyte apoptosis.
Cell death plays a critical role in the generation of an effective immune system. During maturation T lymphocytes are generated, censored and eliminated in the thymus. These events are temporally associated with developmental changes in the levels of transcription factors including NFAT. The NFAT transcription factor (nuclear factor of activated T cells) is implicated in the regulation of T-lymphocyte proliferation and transcriptional activation of genes encoding lymphokines. It has been demonstrated that discontinuities in the inducibility of NFAT and AP-1 transcription factors occur during transition of immature thymocytes into cortical thymocytes which are eliminated by apoptosis. To understand the molecular basis of these developmental intrathymic changes, we studied DNA-binding activities of transcription factors during dexamethasone-induced apoptosis of immature thymocytes. We observed a specific loss of NFAT DNA-binding activity after dexamethasone treatment. It correlated with a selective disappearance of one out of two AP-1 complexes. Our data suggest that NFAT complex is a possible target in dexamethasone-induced apoptosis.
Wisniewska
M
M
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Stanczyk
M
M
Grzelakowska-Sztabert
B
B
Kaminska
B
B
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology*; D014157:Transcription Factors / Q000502:physiology*
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D007376:Interleukin-2; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D003907:Dexamethasone; D004247:DNA