Expression and induction of nuclear factor-kappa B-related proteins in thymocytes.
Thymocytes mature in response to the cues from the thymic micro-environment, which regulate stage-specific gene expression during development. We find that several proteins that bind the kappa B sequence in vitro are constitutively activated in freshly isolated thymocytes. These include the rel-related p50 homodimers, p50/p65 heterodimers, low levels of c-rel, and two other factors that may be thymus specific. Disruption of the thymic micro-environment resulted in loss of DNA-binding, suggesting that lymphocyte-stromal cell interactions induce and maintain these proteins in a DNA-binding form. Phorbol ester and ionomycin treatment induced p50, p65, and p68 c-rel kappa B DNA-binding activity. Expression of p68 c-rel protein, but not p50 or p65, was suppressed by the immunosuppressive drug FK506. Because FK506 specifically inhibits the appearance of mature single-positive thymocytes, gene expression regulated by p68 c-rel may play a role in selection and maturational signals involved in the double-positive to single-positive transition.
Sen
J
J
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02254.
Venkataraman
L
L
Shinkai
Y
Y
Pierce
J W
JW
Alt
F W
FW
Burakoff
S J
SJ
Sen
R
R
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020569:Proto-Oncogene Proteins c-rel; D013601:T-Lymphocytes / Q000378:metabolism*; D016559:Tacrolimus / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000096:biosynthesis*
D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D002118:Calcium; D016559:Tacrolimus