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

نویسندگان

  • Risheng Xu
  • Bindu D Paul
  • Dani R Smith
  • Richa Tyagi
  • Feng Rao
  • A Basit Khan
  • Daniel J Blech
  • M Scott Vandiver
  • Maged M Harraz
  • Prasun Guha
  • Ishrat Ahmed
  • Nilkantha Sen
  • Michela Gallagher
  • Solomon H Snyder
چکیده

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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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 110 40  شماره 

صفحات  -

تاریخ انتشار 2013