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PMID:18445004

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Citation

Hossain, MB, Hosokawa, H, Hasegawa, A, Watarai, H, Taniguchi, M, Yamashita, M and Nakayama, T (2008) Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells. Immunology 125:377-86

Abstract

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.

Links

PubMed PMC2669141 Online version:10.1111/j.1365-2567.2008.02854.x

Keywords

CD4-Positive T-Lymphocytes/immunology; Cell Line; Cytokines/biosynthesis; DNA-Binding Proteins/metabolism; GATA3 Transcription Factor/immunology; GATA3 Transcription Factor/metabolism; HMG-Box Domains/immunology; Humans; Lymphoid Enhancer-Binding Factor 1/immunology; Lymphoid Enhancer-Binding Factor 1/metabolism; Protein Binding; Th2 Cells/immunology; Zinc Fingers/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:LEF1

involved_in

GO:0043392: negative regulation of DNA binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEF1

involved_in

GO:0032696: negative regulation of interleukin-13 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEF1

involved_in

GO:0032713: negative regulation of interleukin-4 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEF1

involved_in

GO:0032714: negative regulation of interleukin-5 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LEF1

enables

GO:0070742: C2H2 zinc finger domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P23771

F

Seeded From UniProt

complete

HUMAN:GATA3

enables

GO:0071837: HMG box domain binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UJU2

F

Seeded From UniProt

complete


See also

References

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