TY - JOUR
T1 - Importin beta plays an essential role in the regulation of the LysRS-Ap4A pathway in immunologically activated mast cells
AU - Carmi-Levy, Irit
AU - Motzik, Alex
AU - Ofir-Birin, Yifat
AU - Yagil, Zohar
AU - Yang, Christopher Maolin
AU - Kemeny, David Michael
AU - Han, Jung Min
AU - Kim, Sunghoon
AU - Kay, Gillian
AU - Nechushtan, Hovav
AU - Suzuki, Ryo
AU - Rivera, Juan
AU - Razin, Ehud
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79956094884&partnerID=8YFLogxK
U2 - 10.1128/MCB.01159-10
DO - 10.1128/MCB.01159-10
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C2 - 21402779
AN - SCOPUS:79956094884
SN - 0270-7306
VL - 31
SP - 2111
EP - 2121
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 10
ER -