Concerted action of Helios and Ikaros controls the expression of the inositol 5-phosphatase SHIP

Jukka Alinikula (Corresponding Author), Pekka Kohonen, Kalle-Pekka Nera, Olli Lassila

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2599-2607
JournalEuropean Journal of Immunology
Volume40
Issue number9
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Keywords

  • BCR signaling
  • Helios
  • Ikaros
  • SHIP

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