Inositol phosphate multikinase dependent transcriptional control.

Published

Journal Article

Production of lipid-derived inositol phosphates including IP4 and IP5 is an evolutionarily conserved process essential for cellular adaptive responses that is dependent on both phospholipase C and the inositol phosphate multikinase Ipk2 (also known as Arg82 and IPMK). Studies of Ipk2, along with Arg82 prior to demonstrating its IP kinase activity, have provided an important link between control of gene expression and IP metabolism as both kinase dependent and independent functions are required for proper transcriptional complex function that enables cellular adaptation in response to extracellular queues such as nutrient availability. Here we define a promoter sequence cis-element, 5'-CCCTAAAAGG-3', that mediates both kinase-dependent and independent functions of Ipk2. Using a synthetic biological strategy, we show that proper gene expression in cells lacking Ipk2 may be restored through add-back of two components: IP4/IP5 production and overproduction of the MADS box DNA binding protein, Mcm1. Our results are consistent with a mechanism by which Ipk2 harbors a dual functionality that stabilizes transcription factor levels and enzymatically produces a small molecule code, which together coordinate control of biological processes and gene expression.

Full Text

Duke Authors

Cited Authors

  • Hatch, AJ; Odom, AR; York, JD

Published Date

  • May 2017

Published In

Volume / Issue

  • 64 /

Start / End Page

  • 9 - 19

PubMed ID

  • 28342784

Pubmed Central ID

  • 28342784

Electronic International Standard Serial Number (EISSN)

  • 2212-4934

International Standard Serial Number (ISSN)

  • 2212-4926

Digital Object Identifier (DOI)

  • 10.1016/j.jbior.2017.03.001

Language

  • eng