Transcriptional regulation of SLP-76 family hematopoietic cell adaptor MIST/Clnk by STAT5

Biochemical and Biophysical Research Communications
H SasanumaRyo Goitsuka

Abstract

SLP-76-related adaptor protein MIST (also called Clnk) is expressed in a variety of cytokine-dependent hematopoietic cell lines of myeloid and lymphoid origin as well as some cytokine-independent mast cell lines. To understand the molecular mechanisms underlying the MIST gene expression, we have characterized the 5'-flanking region of the mouse MIST gene. We have identified an enhancer region (-773 to -709), which is active in P815 mast cells expressing the endogenous MIST gene, but not in EL-4 T cells lacking MIST expression. Outside of this enhancer region, one STAT element present in the MIST promoter (-44 to -36) was found to bind STAT5A when IC-2 mast cells were stimulated with IL-3. Mutation of this STAT element did not affect basal MIST promoter activity in P815 mast cells, but was required for STAT5-mediated activation of the MIST promoter. Furthermore, endogenous MIST gene expression was induced in mast cells by a constitutively activated form of STAT5A, but not by an active mutant of c-Kit receptor. These findings suggest that STAT5 is involved in cytokine-mediated up-regulation of MIST gene expression, probably in collaboration with other lineage-specific transcription factors that promote basal MIST expression in ma...Continue Reading

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Citations

Jun 11, 2010·Genes and Immunity·J K MoralesJ J Ryan
May 27, 2015·Biochemical and Biophysical Research Communications·Meng XuHuamin Zhou
Sep 2, 2008·Immunological Reviews·Sabrina RichardsEdward A Clark

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