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Mol Cell Biol. 2011 May;31(10):2111-21. doi: 10.1128/MCB.01159-10. Epub 2011 Mar 14.

Importin beta plays an essential role in the regulation of the LysRS-Ap(4)A pathway in immunologically activated mast cells.

Author information

1
Department of Biochemistry and Molecular Biology, The Institute for Medical Research-Israel-Canada, The Hebrew University-Hadassah Medical School, POB 12272, Jerusalem 91120, Israel.

Abstract

We recently reported that diadenosine tetraphosphate hydrolase (Ap(4)A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap(4)A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap(4)A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap(4)A hydrolase nuclear translocation and affected the local concentration of Ap(4)A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap(4)A hydrolase, which changed the hydrolytic activity of the enzyme.

PMID:
21402779
PMCID:
PMC3133347
DOI:
10.1128/MCB.01159-10
[Indexed for MEDLINE]
Free PMC Article

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