Importin beta plays an essential role in the regulation of the LysRS-Ap4A pathway in immunologically activated mast cells

Irit Carmi-Levy, Alex Motzik, Yifat Ofir-Birin, Zohar Yagil, Christopher Maolin Yang, David Michael Kemeny, Jung Min Han, Sunghoon Kim, Gillian Kay, Hovav Nechushtan, Ryo Suzuki, Juan Rivera, Ehud Razin

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10 Citations (Scopus)

Abstract

We recently reported that diadenosine tetraphosphate hydrolase (Ap4A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap4A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap4A 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 Ap4A hydrolase nuclear translocation and affected the local concentration of Ap4A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap4A hydrolase, which changed the hydrolytic activity of the enzyme.

Original languageEnglish
Pages (from-to)2111-2121
Number of pages11
JournalMolecular and cellular biology
Volume31
Issue number10
DOIs
Publication statusPublished - 2011 May

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Carmi-Levy, I., Motzik, A., Ofir-Birin, Y., Yagil, Z., Yang, C. M., Kemeny, D. M., Han, J. M., Kim, S., Kay, G., Nechushtan, H., Suzuki, R., Rivera, J., & Razin, E. (2011). Importin beta plays an essential role in the regulation of the LysRS-Ap4A pathway in immunologically activated mast cells. Molecular and cellular biology, 31(10), 2111-2121. https://doi.org/10.1128/MCB.01159-10