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Publication : Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction.

First Author  Xu R Year  2013
Journal  Proc Natl Acad Sci U S A Volume  110
Issue  40 Pages  16181-6
PubMed ID  24043835 Mgi Jnum  J:201129
Mgi Id  MGI:5511067 Doi  10.1073/pnas.1315551110
Citation  Xu R, et al. (2013) Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction. Proc Natl Acad Sci U S A 110(40):16181-16186
abstractText  Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters. Interestingly, IPMK regulation of CBP recruitment and IEG induction does not require its catalytic activities. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously expressed, its epigenetic regulation of IEGs may influence diverse nonneural and neural biologic processes.
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