title: Early growth response 1 (EGR-1) is a transcriptional regulator of mitochondrial carrier homolog 1 (MTCH 1)/presenilin 1-associated protein (PSAP).
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.
authors.affiliation: Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Zaragoza, Spain; Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, Zaragoza, Spain. Electronic address: maria.a.nelo.b@gmail.com.
authors.forename: María Alejandra
authors.initials: MA
authors.lastname: Nelo-Bazán
authors.affiliation: Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Zaragoza, Spain; Department of Animal Production and Food Science and Technology, University of Zaragoza, Spain. Electronic address: platmu@unizar.es.
authors.forename: Pedro
authors.initials: P
authors.lastname: Latorre
authors.affiliation: Department of Molecular Biology, University of Cantabria, IDIVAL, Santander, Cantabria, Spain. Electronic address: boladoca@outlook.es.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bolado-Carrancio
authors.affiliation: Department of Internal Medicine, Hospital U. Marqués de Valdecilla-IDIVAL University of Cantabria, 39008 Santander, Cantabria, Spain. Electronic address: f.perezcampo@unican.es.
authors.forename: Flor M
authors.initials: FM
authors.lastname: Pérez-Campo
authors.affiliation: Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Zaragoza, Spain; Instituto de Química Física Rocasolano, CSIC, Madrid, Spain; Zaragoza Scientific Center for Advanced Modeling (ZCAM), Universidad de Zaragoza, Spain; Departamento de Física Teórica, Universidad de Zaragoza, Spain; Unidad Asociada IQFR-BIFI, Madrid-Zaragoza, Spain. Electronic address: pablo.echenique.robba@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Echenique-Robba
authors.affiliation: Department of Molecular Biology, University of Cantabria, IDIVAL, Santander, Cantabria, Spain. Electronic address: josecarlos.rodriguez@unican.es.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Rodríguez-Rey
authors.affiliation: Institute for Biocomputation and Physics of Complex Systems, University of Zaragoza, Zaragoza, Spain; Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, Zaragoza, Spain; Unidad Asociada IQFR-BIFI, Madrid-Zaragoza, Spain. Electronic address: carrode@unizar.es.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Carrodeguas
mesh_terms: D001665:Binding Sites; D004317:Doxorubicin / Q000494:pharmacology; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C402222:MTCH1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D004317:Doxorubicin
keywords: Apoptosis; Cell death; Early growth response 1 (EGR-1); Gene expression; Mitochondria; Mitochondrial carrier homolog 1 (MTCH1); Transcriptional regulation