Sumoylation 對於c-Maf調控細胞激素之研究
The Role of Sumoylation on c-Maf in Cytokine Regulation
Date Issued
2007
Date
2007
Author(s)
Tsai, Pei-Yun
DOI
en-US
Abstract
Naïve CD4+ T helper (Th) cells can be polarized towards either the Th1 or the Th2 subset. Interleukin-4 (IL-4) is crucial for the differentiation toward Th2 effector cells that promote humoral immunity and provide protection against intestinal helminthes. Many transcription factors are involved in the regulation of the gene encoding IL-4. Notably, c-Maf, a basic-leucine zipper protein belongs to the MAF family, has been proved to be the IL-4 gene-specific transactivator. On the other hand, c-Maf also acts as a potent activator of IL-10 gene and an inhibitor of IL-12 p40 and p35 gene expression in monocytes and macrophages. Besides, c-Maf was reported to be involved in lens development and oncogenesis. These phenomena implied that some cell-type specific factors would interact with c-Maf and thus to regulate its function.
Our lab has identified two c-Maf interacting factors, UBC9, and PIAS1, by the yeast two-hybrid system using c-Maf as the bait. The two proteins are involved in the sumoylation. Therefore, we assume that the sumoylation might play some important roles in the function of c-Maf and further regulate IL-4 production in Th2 cells. To study this issue, we want to investigate whether the sumoylation would occur in vivo and dissect how the post translational modifications affect c-Maf function.
In this study, we found that c-Maf could undergo sumoylation in HEK293T and DO11.10 T cells. The functional analysis of sumoylated c-Maf was also performed by luciferase assay in HEK293T and DO11.10 cells indicating that sumoylation acts as a negative regulator to c-Maf in IL-4 transactivation. Sumoylated c-Maf could be revealed in cytosol. In addition, enhanced DNA binding ability could be observed when c-Maf without sumoylation. The two phenomena might contribute to reduced IL-4 gene transactivation by sumoyalted c-Maf.
Subjects
細胞激素
c-Maf
Type
other
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