Arginine Transcriptional Response Does Not Require Inositol Phosphate Synthesis

Bosch, Daniel; Saiardi, Adolfo

doi:10.1074/jbc.m112.384255

Cited by 29 publications

(34 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, our findings that IPMK stimulated p53-mediated transcription independently of its catalytic function is consistent with evidence that its homolog in yeast does not require its catalytic metabolites to enhance transcription mediated by Mcm1 in response to arginine (49–51). This noncatalytic action of IPMK is also supported by observations that IPMK stabilizes the amino acid–induced mTORC1 independently of any kinase activity (19).…”

Section: Discussionsupporting

confidence: 90%

Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

Sen

Paul

et al. 2013

Sci. Signal.

View full text Add to dashboard Cite

The tumor suppressor protein p53 is a critical stress response transcription factor that induces the expression of genes leading to cell cycle arrest, apoptosis, and tumor suppression. We found that mammalian inositol polyphosphate multikinase (IPMK) stimulated p53-mediated transcription by binding to p53 and enhancing its acetylation by the acetyltransferase p300 independently of its inositol phosphate and lipid kinase activities. Genetic or RNA interference (RNAi)–mediated knockdown of IPMK resulted in decreased activation of p53, decreased recruitment of p53 and p300 to target gene promoters, abrogated transcription of p53 target genes, and enhanced cell viability. Additionally, blocking the IPMK-p53 interaction decreased the extent of p53-mediated transcription. These results suggest that IPMK acts as a transcriptional coactivator for p53 and that it is an integral part of the p53 transcriptional complex facilitating cell death.

show abstract

Section: Discussionsupporting

confidence: 90%

Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

Sen

Paul

et al. 2013

Sci. Signal.

View full text Add to dashboard Cite

show abstract

“…Within the nucleus, yeast IPMK (also known as Arg82) regulates genes responsive to arginine and phosphate disposition (33). Although considerable debate has centered on the role of IPMK's catalytic metabolites in yeast transcriptional regulation (34)(35)(36), recent complementation experiments reveal that arginine gene transcription does not require IPMK's catalytic activity (37). This is in contrast with PHO5 gene transcription, which requires IPMK's IP3-kinase functionality (38).…”

Section: Discussioncontrasting

confidence: 39%

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

Paul

Smith

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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.inositol phosphates | learning

show abstract

“…The present study describes a noncatalytic role of IPMK as a transcriptional coactivator for SRF, analogous to such influences upon p53 (14) and CBP (16). Similar transcriptional regulatory activities occur in yeast, where IPMK regulates genes involved in arginine and phosphate disposition, actions that also appear to be independent of catalytic activity (63). However, another noncatalytic action of IPMK is evident in its binding to mTOR to stabilize the mTORC1 complex and enhance protein translation (6).…”

Section: Discussionmentioning

confidence: 96%

Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes

Kim¹,

Tyagi

Lee³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes.

show abstract

Arginine Transcriptional Response Does Not Require Inositol Phosphate Synthesis

Cited by 29 publications

References 58 publications

Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

Inositol Polyphosphate Multikinase Is a Coactivator of p53-Mediated Transcription and Cell Death

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

Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes

Contact Info

Product

Resources

About