First Author | Hossain MB | Year | 2008 |
Journal | Immunology | Volume | 125 |
Issue | 3 | Pages | 377-86 |
PubMed ID | 18445004 | Mgi Jnum | J:144450 |
Mgi Id | MGI:3830943 | Doi | 10.1111/j.1365-2567.2008.02854.x |
Citation | Hossain MB, et al. (2008) Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells. Immunology 125(3):377-86 |
abstractText | 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. |