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

Friederike Berberich-Siebelt^2,*, Ingolf Berberich, Mindaugas Andrulis, Brigitte Santner-Nanan^3,, Mithilesh K. Jha^4,*, Stefan Klein-Hessling^*, Anneliese Schimpl and Edgar Serfling^*

^* Department of Molecular Pathology, Institute of Pathology, and Institute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany

The transcription factor C/EBP transactivates the IL-4 gene in murine T lymphocytes and facilitates Th2 cell responses. In this study, we demonstrate that C/EBP also acts as a repressor of T cell proliferation. By binding to the c-myc promoter(s), C/EBP represses c-Myc expression and, therefore, arrests T cells in the G₁ phase of the cell cycle. For C/EBP-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/EBP. Whereas sumoylation does not affect the C/EBP-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/EBP 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/EBP.

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