Journal Article

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

Cha, Jiyoung Y., Kim, Eunha, Beon, Jiyoon, Kim, Young-ran, Snyder, Solomon H., Po Yu Chen, Kim, Seyun, Lee, Joo-Young, Park, Jina, Tyagi, Richa

2013

Overview

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.

• Publisher: National Academy of Sciences,NATIONAL ACADEMY OF SCIENCES,National Acad Sciences
• Subject: 1-phosphatidylinositol 4-kinase / Animals / binding proteins / Binding sites / Biological and medical sciences / Biological Sciences / blood serum / Catalytic activity / Chromatin Immunoprecipitation / DNA Primers - genetics / E1A-Associated p300 Protein - metabolism / Exons / Fundamental and applied biological sciences. Psychology / Gene expression / Gene expression regulation / Genes / Genes, Immediate-Early - genetics / Genes, Immediate-Early - physiology / HEK293 cells / Image Processing, Computer-Assisted / Immediate early genes / Immunoblotting / Inositols / mammals / Mice / Mice, Knockout / Microarray Analysis / Neurons / Phosphates / Phosphorylation / Phosphotransferases (Alcohol Group Acceptor) - genetics / Phosphotransferases (Alcohol Group Acceptor) - metabolism / Polyphosphates / Proteins / Serum Response Factor - metabolism / Signal Transduction - genetics / Signal Transduction - physiology / TOR Serine-Threonine Kinases - metabolism / transcription (genetics) / transcription factors / Transcriptional Activation - genetics / Transcriptional Activation - physiology / tumor suppressor protein p53 / Tumor Suppressor Protein p53 - metabolism / Vertebrates: nervous system and sense organs