Early growth response 1 (EGR-1) is a transcriptional regulator of mitochondrial carrier homolog 1 (MTCH 1)/presenilin 1-associated protein (PSAP)

Gene. 2016 Mar 1;578(1):52-62. doi: 10.1016/j.gene.2015.12.014. Epub 2015 Dec 9.

Abstract

Attempts to elucidate the cellular function of MTCH1 (mitochondrial carrier homolog 1) have not yet rendered a clear insight into the function of this outer mitochondrial membrane protein. Classical biochemical and cell biology approaches have not produced the expected outcome. In vitro experiments have indicated a likely role in the regulation of cell death by apoptosis, and its reported interaction with presenilin 1 suggests a role in the cellular pathways in which this membrane protease participates, nevertheless in vivo data are missing. In an attempt to identify cellular pathways in which this protein might participate, we have studied its promoter looking for transcriptional regulators. We have identified several putative binding sites for EGR-1 (Early growth response 1; a protein involved in growth, proliferation and differentiation), in the proximal region of the MTCH1 promoter. Chromatin immunoprecipitation showed an enrichment of these sequences in genomic DNA bound to EGR-1 and transient overexpression of EGR-1 in cultured HEK293T cells induces an increase of endogenous MTCH1 levels. We also show that MTCH1 levels increase in response to treatment of cells with doxorubicin, an apoptosis inducer through DNA damage. The endogenous levels of MTCH1 decrease when EGR-1 levels are lowered by RNA interference. Our results indicate that EGR-1 is a transcriptional regulator of MTCH1 and give some clues about the cellular processes in which MTCH1 might participate.

Keywords: Apoptosis; Cell death; Early growth response 1 (EGR-1); Gene expression; Mitochondria; Mitochondrial carrier homolog 1 (MTCH1); Transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Doxorubicin / pharmacology
  • Early Growth Response Protein 1 / metabolism*
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism*
  • Promoter Regions, Genetic

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • MTCH1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Doxorubicin