Journal
IMMUNOLOGY
Volume 125, Issue 3, Pages 377-386Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2567.2008.02854.x
Keywords
GATA-3; HMG box; LEF-1; Th2; Wnt/beta-catenin
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (Japan) [17016010, 17390139, 18590466, 19590491, 19591609, 19659121, 18890046]
- Ministry of Health, Labor and Welfare (Japan)
- Japan Health Science Foundation
- Kanae Foundation
- Uehara Memorial Foundation
- Mochida Foundation
- Yasuda Medical Foundation
- Astellas Foundation
- Sagawa Foundation
- Grants-in-Aid for Scientific Research [17390139, 19659121, 18890046, 19590491, 19591609, 18590466] Funding Source: KAKEN
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GATA-3 is the master transcription factor for T helper 2 (Th2) cell differentiation and is critical for the expression of Th2 cytokines. Little is known, however, about the nature of the functional molecular complexes of GATA-3. We identified a high-mobility group (HMG)-box type transcription factor, lymphoid enhancer factor 1 (LEF-1), in the GATA-3 complex present in Th2 cells using a Flag-calmodulin-binding peptide (CBP)-tag based proteomics method. The interaction between GATA-3 and LEF-1 was confirmed by co-immunoprecipitation experiments using LEF-1-introduced T-cell lineage TG40 cells. The HMG-box domain of LEF-1 and two zinc finger domains of GATA-3 were found to be important for the physical association. The introduction of LEF-1 into developing Th2 cells resulted in the suppression of Th2 cytokine production. The suppression was significantly lower in the cells into which a HMG-box-deleted LEF-1 mutant was introduced. Moreover, LEF-1 inhibited the binding activity of GATA-3 to the interleukin (IL)-5 promoter. These results suggest that LEF-1 is involved in the GATA-3 complex, while also regulating the GATA-3 function, such as the induction of Th2 cytokine expression via the inhibition of the DNA-binding activity of GATA-3.
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