Communicated by: Shunsuke Ishii
Transgenic over-expression of MafK suppresses T cell proliferation and function in vivo
Article first published online: 20 DEC 2001
Genes to Cells
Volume 6, Issue 12, pages 1055–1066, December 2001
How to Cite
Yoh, K., Sugawara, T., Motohashi, H., Takahama, Y., Koyama, A., Yamamoto, M. and Takahashi, S. (2001), Transgenic over-expression of MafK suppresses T cell proliferation and function in vivo. Genes to Cells, 6: 1055–1066. doi: 10.1046/j.1365-2443.2001.00489.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received: 9 July 2001Accepted: 27 September 2001
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.