MLX Is a Transcriptional Repressor of the Mammalian Golgi Stress Response

Cell Struct Funct. 2016 Jul 30;41(2):93-104. doi: 10.1247/csf.16005. Epub 2016 Jun 2.

Abstract

The Golgi stress response is a homeostatic mechanism that controls the capacity of the Golgi apparatus in accordance with cellular demands. When the capacity of the Golgi apparatus becomes insufficient (Golgi stress), transcription levels of Golgi-related genes encoding glycosylation enzymes, a Golgi structural protein, and components of vesicular transport are upregulated through a common cis-acting enhancer-the Golgi apparatus stress response element (GASE). Here, we identified the transcription factor MLX as a GASE-binding protein. MLX resides in the cytoplasm and does not bind to GASE in normal growth conditions, whereas MLX translocates into the nucleus and specifically binds to GASE in response to Golgi stress. Suppression of MLX expression increased transcriptional induction of target genes of the Golgi stress response, whereas overexpression of MLX reduced GASE-binding of TFE3 as well as transcriptional induction from GASE, suggesting that MLX is a transcriptional repressor of the mammalian Golgi stress response.

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / antagonists & inhibitors
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Blotting, Northern
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation / genetics
  • Genes, Reporter / genetics
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Microscopy, Fluorescence
  • Protein Binding
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Real-Time Polymerase Chain Reaction
  • Response Elements / genetics

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MLX protein, human
  • RNA, Messenger
  • RNA, Small Interfering