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The Journal of Immunology, 2006, 176: 4843-4851.
Copyright © 2006 by The American Association of Immunologists

SUMOylation Interferes with CCAAT/Enhancer-Binding Protein beta-Mediated c-myc Repression, but Not IL-4 Activation in T Cells1

Friederike Berberich-Siebelt2,*, Ingolf Berberich{ddagger}, Mindaugas Andrulis{dagger}, Brigitte Santner-Nanan3,{ddagger}, Mithilesh K. Jha4,*, Stefan Klein-Hessling*, Anneliese Schimpl{ddagger} and Edgar Serfling*

* Department of Molecular Pathology, {dagger} Institute of Pathology, and {ddagger} Institute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany

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.




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