Transgenic over‐expression of MafK suppresses T cell proliferation and function in vivo

This is the authors' abstract. We don't add key points for this paper.

BACKGROUND: The small Maf proteins regulate gene transcription from Maf recognition elements (MARE). These proteins do not contain a canonical transactivation domain. Depending upon the ratio of small Maf proteins to their partner proteins, which either possess a transactivation domain or not, transcription can be switched on or off. RESULTS: Transgenic mice were generated which over-express the small Maf family member MafK, specifically in the T cell lineage. It was our expectation that the high level of MafK would shift the balance to the formation of MafK homodimer and thereby repress MARE-dependent transcription. The transgenic mice had a shortened life span because of Pneumocystis carinii pneumonia and displayed a decrease in thymocytes and lower IL-2 and IL-4 mRNA expression levels. Analyses by electrophoretic gel mobility shift assay revealed that over-expressed MafK could interact with the proximal AP-1 sequence of IL-2 and the MARE in the IL-4 promoter region. CONCLUSION: These results indicate that when over-expressed, MafK binds to a MARE-like sequence and represses MARE-dependent transcription. Consequently, T cell proliferation and cytokine secretion are affected. The MafK homodimer serves as an important molecular probe for evaluating the role played by cis-acting MAREs in the proliferation and function of T cells.