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


CONCLUSIONS
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.
Yoh
K
K
Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
Sugawara
T
T
Motohashi
H
H
Takahama
Y
Y
Koyama
A
A
Yamamoto
M
M
Takahashi
S
S
D000818:Animals; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D050985:MafK Transcription Factor; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D011020:Pneumonia, Pneumocystis / Q000209:etiology / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D007074:Immunoglobulin G; D007376:Interleukin-2; D050985:MafK Transcription Factor; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D015847:Interleukin-4