Inositol phosphate multikinase dependent transcriptional control.
Production of lipid-derived inositol phosphates including IP4and IP5is 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/IP5production 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.
Departments of Pharmacology and Cancer Biology and of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Ace J
AJ
Hatch
Departments of Pharmacology and Cancer Biology and of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Audrey R
AR
Odom
Departments of Pharmacology and Cancer Biology and of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA; Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, TN 37232-0146, USA. Electronic address: john.york@vanderbilt.edu.
John D
JD
York
D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D007295:Inositol Phosphates / Q000378:metabolism*; D026341:Minichromosome Maintenance 1 Protein / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
D007295:Inositol Phosphates; C498030:MCM1 protein, S cerevisiae; D026341:Minichromosome Maintenance 1 Protein; D029701:Saccharomyces cerevisiae Proteins; C425775:ARG82 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); D010738:Type C Phospholipases