Soluble syntaxin 3 functions as a transcriptional regulator
| Autor: | Christine Winterstein, Adrian J. Giovannone, Matthew A. Lalli, Julie E. Baggs, Mimi Xu, Elena Reales, Thomas Weimbs, Pallavi Bhattaram, Seng Hui Low, John B. Hogenesch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
membrane fusion Transcription coregulator Medical and Health Sciences Biochemistry syntaxin signaling Madin Darby Canine Kidney Cells Chlorocebus aethiops 2.1 Biological and endogenous factors Aetiology Cancer biology Chemistry Qa-SNARE Proteins membrane trafficking Biological Sciences beta Karyopherins Activating transcription factor 2 Transmembrane protein Cell biology COS Cells Adenovirus E1A Proteins Signal transduction signal transduction Biotechnology Protein Binding Signal Transduction Biochemistry & Molecular Biology SNARE proteins splice variant 1.1 Normal biological development and functioning alternative splicing 03 medical and health sciences Dogs Underpinning research Proto-Oncogene Proteins Breast Cancer Genetics Animals Humans Molecular Biology Transcription factor transcriptional regulator Cell Proliferation Cell Nucleus Proto-Oncogene Proteins c-ets Alternative splicing Cell Biology Syntaxin 3 transcription coregulator 030104 developmental biology HEK293 Cells Gene Expression Regulation Solubility Hela Cells Chemical Sciences biology.protein Nuclear transport Caco-2 Cells HeLa Cells |
| Zdroj: | The Journal of biological chemistry, vol 293, iss 15 |
| Popis: | Syntaxins are a conserved family of SNARE proteins and contain C-terminal transmembrane anchors required for their membrane fusion activity. Here we show that Stx3 (syntaxin 3) unexpectedly also functions as a nuclear regulator of gene expression. We found that alternative splicing creates a soluble isoform that we termed Stx3S, lacking the transmembrane anchor. Soluble Stx3S binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors, including ETV4 (ETS variant 4) and ATF2 (activating transcription factor 2). Stx3S is differentially expressed in normal human tissues, during epithelial cell polarization, and in breast cancer versus normal breast tissue. Inhibition of endogenous Stx3S expression alters the expression of cancer-associated genes and promotes cell proliferation. Similar nuclear-targeted, soluble forms of other syntaxins were identified, suggesting that nuclear signaling is a conserved, novel function common among these membrane-trafficking proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|