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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Acid Anhydride Hydrolases / metabolism*
-
Animals
-
Blotting, Western
-
Cell Line, Tumor
-
Cell Nucleus / metabolism*
-
Cells, Cultured
-
Dinucleoside Phosphates / analysis
-
Flow Cytometry
-
Gene Expression
-
Immunoglobulin E / immunology
-
Immunoprecipitation
-
Lysine-tRNA Ligase / genetics
-
Lysine-tRNA Ligase / metabolism*
-
Mast Cells / immunology*
-
Mast Cells / metabolism
-
Mice
-
Microphthalmia-Associated Transcription Factor / genetics
-
Polymerase Chain Reaction
-
Protein Processing, Post-Translational
-
RNA Interference
-
RNA, Small Interfering
-
Rats
-
beta Karyopherins / genetics
-
beta Karyopherins / metabolism*
Substances
-
Dinucleoside Phosphates
-
Microphthalmia-Associated Transcription Factor
-
RNA, Small Interfering
-
beta Karyopherins
-
Immunoglobulin E
-
diadenosine tetraphosphate
-
Acid Anhydride Hydrolases
-
bis(5'-nucleosyl)tetraphosphatase (asymmetrical)
-
Lysine-tRNA Ligase