SUMOylation interferes with CCAAT/enhancer-binding protein beta-mediated c-myc repression, but not IL-4 activation in T cells.
The transcription factor C/EBPbeta transactivates the IL-4 gene in murine T lymphocytes and facilitates Th2 cell responses. In this study, we demonstrate that C/EBPbeta also acts as a repressor of T cell proliferation. By binding to the c-myc promoter(s), C/EBPbeta represses c-Myc expression and, therefore, arrests T cells in the G1 phase of the cell cycle. For C/EBPbeta-mediated repression, the integrity of its N-terminal transactivation domain is essential whereas the central regulatory domain is dispensable. This central regulatory domain is sumoylated in vivo which leads to an alteration of the activity of C/EBPbeta. Whereas sumoylation does not affect the C/EBPbeta-mediated activation of the IL-4 gene, it relieves its repressive effect on c-Myc expression and T cell proliferation. Similar to several other transcription factors, sumoylation redistributes nuclear C/EBPbeta and targets it to pericentric heterochromatin. These results suggest an important role of sumoylation in adjusting the finely tuned balance between proliferation and differentiation in peripheral T cells which is controlled by C/EBPbeta.
Berberich-Siebelt
Friederike
F
Department of Molecular Pathology, University of Wuerzbrug, Germany. path230@mail.uni-wuerzburg.de
Berberich
Ingolf
I
Andrulis
Mindaugas
M
Santner-Nanan
Brigitte
B
Jha
Mithilesh K
MK
Klein-Hessling
Stefan
S
Schimpl
Anneliese
A
Serfling
Edgar
E
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D016259:Genes, myc; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018448:Models, Immunological; D011401:Promoter Regions, Genetic; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013489:Suppression, Genetic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015533:Transcriptional Activation
D022782:CCAAT-Enhancer-Binding Protein-beta; D025841:Small Ubiquitin-Related Modifier Proteins; D015847:Interleukin-4; D004247:DNA