SUMOylation interferes with CCAAT/enhancer-binding protein β-mediated c-myc repression, but not IL-4 activation in T cells

F Berberich-Siebelt, I Berberich, M Andrulis… - The Journal of …, 2006 - journals.aai.org
F Berberich-Siebelt, I Berberich, M Andrulis, B Santner-Nanan, MK Jha, S Klein-Hessling…
The Journal of Immunology, 2006journals.aai.org
The transcription factor C/EBPβ transactivates the IL-4 gene in murine T lymphocytes and
facilitates Th2 cell responses. In this study, we demonstrate that C/EBPβ also acts as a
repressor of T cell proliferation. By binding to the c-myc promoter (s), C/EBPβ represses c-
Myc expression and, therefore, arrests T cells in the G 1 phase of the cell cycle. For C/EBPβ-
mediated repression, the integrity of its N-terminal transactivation domain is essential
whereas the central regulatory domain is dispensable. This central regulatory domain is …
Abstract
The transcription factor C/EBPβ transactivates the IL-4 gene in murine T lymphocytes and facilitates Th2 cell responses. In this study, we demonstrate that C/EBPβ also acts as a repressor of T cell proliferation. By binding to the c-myc promoter (s), C/EBPβ represses c-Myc expression and, therefore, arrests T cells in the G 1 phase of the cell cycle. For C/EBPβ-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/EBPβ. Whereas sumoylation does not affect the C/EBPβ-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/EBPβ 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/EBPβ.
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