title: Activation of AHR mediates the ubiquitination and proteasome degradation of c-Fos through the induction of Ubcm4 gene expression.
abstract: The ubiquitin-proteasome system (UPS) is a specific, non-lysosomal pathway responsible for the controlled degradation of abnormal and short-half-life proteins. Despite its relevance in cell homeostasis, information regarding control of the UPS component gene expression is lacking. Data from a recent study suggest that the aryl hydrocarbon receptor (AHR), a ligand-dependent transcription factor, might control the expression of several genes encoding for UPS proteins. Here, we showed that activation of AHR by TCDD and β-naphthoflavone (β-NF) results in Ubcm4 gene induction accompanied by an increase in protein levels. UbcM4 is an ubiquitin-conjugating enzyme or E2 protein that in association with ubiquitin ligase enzymes or E3 ligases promotes the ubiquitination and 26S proteasome-mediated degradation of different proteins, including p53, c-Myc, and c-Fos. We also present data demonstrating increased c-Fos ubiquitination and proteasomal degradation through the AHR-mediated induction of UbcM4 expression. The present study shows that AHR modulates the degradation of proteins involved in cell cycle control, consistent with previous reports demonstrating an essential role of the AHR in cell cycle regulation.
authors: Departamento de Biología Celular, CINVESTAV-IPN, Av. IPN 2508, C.P. 07360 Mexico D.F., Mexico.
authors: A
authors: A
authors: Mejía-García
authors: Departamento de Biología Celular, CINVESTAV-IPN, Av. IPN 2508, C.P. 07360 Mexico D.F., Mexico.
authors: E
authors: E
authors: González-Barbosa
authors: Departamento de Biología Celular, CINVESTAV-IPN, Av. IPN 2508, C.P. 07360 Mexico D.F., Mexico.
authors: C
authors: C
authors: Martínez-Guzmán
authors: Unidad Periférica de Neurociencias, Facultad de Medicina Universidad Nacional Autónoma de México/Instituto Nacional de Neurología y Neurocirugía, Av. Insurgentes Sur 3877, C.P. 14269 México D.F., Mexico.
authors: M A
authors: MA
authors: Torres-Ramos
authors: Inbiomed, Parque Tecnológico de Miramón. Mikeletegi 81, San Sebastián 2009, Spain.
authors: M S
authors: MS
authors: Rodríguez
authors: Unidad de Microarreglos de DNA, Universidad Nacional Autónoma de México, Av. Universidad 3000, C.P. 04510 Mexico D.F., Mexico.
authors: S
authors: S
authors: Guzmán-León
authors: Departamento de Biología Celular, CINVESTAV-IPN, Av. IPN 2508, C.P. 07360 Mexico D.F., Mexico. Electronic address: gazuela@cinvestav.mx.
authors: G
authors: G
authors: Elizondo
mesh_terms: D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D010957:Plasmids / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects*; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D054875:Ubiquitination / Q000187:drug effects*; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D016760:Proto-Oncogene Proteins c-fos; D018336:Receptors, Aryl Hydrocarbon; C471619:UBE2L4 protein, human; D019324:beta-Naphthoflavone; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex
keywords: Aryl hydrocarbon receptor; TCDD; UbcM4; Ubiquitination; c-Fos