CREB function is required for normal thymic cellularity and post-irradiation recovery.
Recent generation of genetically modified Creb1 mutant mice has revealed an important role for CREB (cAMP responsive element binding protein) and the related proteins CREM (cAMP responsive element modulator) and ATF1 (activating transcription factor 1) in cell survival, in agreement with previous studies using overexpression of dominant-negative CREB (dnCREB). CREB and ATF1 are abundantly expressed in T cells and are rapidly activated by phosphorylation when T cells are stimulated through the T cell antigen receptor. We show that T cell-specific loss of CREB in mice, in combination with the loss of ATF1, results in reduced thymic cellularity and delayed thymic recovery following sublethal irradiation but no changes in T cell development or activation. These data show that loss of CREB function has specific effects on thymic T lymphocyte proliferation and homeostasis in vivo.
Baumann
Sven
S
Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Kyewski
Bruno
B
Bleckmann
Susanne C
SC
Greiner
Erich
E
Rudolph
Dorothea
D
Schmid
Wolfgang
W
Ramsay
Robert G
RG
Krammer
Peter H
PH
Schütz
Günther
G
Mantamadiotis
Theo
T
D051697:Activating Transcription Factor 1; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000528:radiation effects; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011995:Recombination, Genetic / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors