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PMID:20602434

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Citation

Alinikula, J, Kohonen, P, Nera, KP and Lassila, O (2010) Concerted action of Helios and Ikaros controls the expression of the inositol 5-phosphatase SHIP. Eur. J. Immunol. 40:2599-607

Abstract

Ikaros family transcription factors have a key role in lymphoid development, and their aberrant function contributes to a multitude of lymphoid malignancies. Ikaros and Helios bind to similar DNA sequences, and Helios associates with Ikaros-containing chromatin remodeling complexes. Previously, we have shown that loss of Ikaros leads to diminished BCR-signaling strength. In this study, we describe a Helios-deficient chicken DT40 B-cell line with a BCR signaling phenotype that is the opposite to that of Ikaros-deficient cells. In contrast to Ikaros-deficient cells, Helios(-/-) B cells exhibit increased calcium release to the cytoplasm after BCR crosslinking, but diminished BCR-induced phosphorylation of signaling molecules. The inositol 5-phosphatase SHIP, an important regulator in several signaling pathways, is differentially expressed in Ikaros- and Helios-deficient cells. In the absence of Ikaros, SHIP is upregulated, whereas Helios deficiency leads to the downregulation of SHIP expression. We also show with ChIP that Ikaros binds to the promoter of the INPP5D gene-encoding SHIP. Considering the critical role of SHIP in the BCR signaling pathway, our findings provide insight into the mechanism of how both Helios and Ikaros are involved in the regulation of BCR signaling.

Links

PubMed Online version:10.1002/eji.200940002

Keywords

Animals; B-Lymphocytes/immunology; B-Lymphocytes/metabolism; B-Lymphocytes/pathology; Calcium Signaling/genetics; Calcium Signaling/immunology; Cell Line; Chickens; Gene Expression Regulation; Gene Knockout Techniques; Ikaros Transcription Factor/genetics; Ikaros Transcription Factor/immunology; Ikaros Transcription Factor/metabolism; Phosphoric Monoester Hydrolases/genetics; Phosphoric Monoester Hydrolases/immunology; Phosphoric Monoester Hydrolases/metabolism; Promoter Regions, Genetic; Protein Binding; Receptors, Antigen, B-Cell/immunology; Signal Transduction/genetics; Signal Transduction/immunology

Significance

Annotations

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

CHICK:IKZF1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:IKZF1

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:IKZF1

part_of

GO:0032993: protein-DNA complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:IKZF1

involved_in

GO:0007204: positive regulation of cytosolic calcium ion concentration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:IKZF1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CHICK:IKZF1

enables

GO:0044212: transcription regulatory region DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CHICK:IKZF1

involved_in

GO:0016049: cell growth

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:IKZF1

involved_in

GO:0002377: immunoglobulin production

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

CHICK:IKZF1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q90W82

involved_in

GO:0051481: negative regulation of cytosolic calcium ion concentration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q90W82

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CHICK:Q90W82

involved_in

GO:0006468: protein phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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