Activation of AHR mediates the ubiquitination and proteasome degradation of c-Fos through the induction of Ubcm4 gene expression

Mejía-García, Alejandro; González-Barbosa, Emmanuel; Martínez-Guzmán, Carmen; Torres-Ramos, Mónica; Rodríguez, Manuel Sánchez; Guzmán-León, Simón; Elizondo, Guillermo

doi:10.1016/j.tox.2015.08.008

Cited by 20 publications

(18 citation statements)

References 44 publications

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“…The cells were grown in 100‐mm dishes with DMEM high glucose medium (Gibco, Carlsbad, CA) supplemented with 10% fetal bovine serum (Gibco, Logan, UT) and 1% antibiotic/antimycotic (Invitrogen, Carlsbad, CA) at 37°C in a humidified incubator with a 5% CO 2 atmosphere. The reporter plasmid pGL4/‐832UbcH7 containing the Ubch7 gene promoter was described previously . SH‐SY5Y cells were cultured in DMEM high glucose medium as described above.…”

Section: Methodsmentioning

confidence: 99%

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TCDD induces UbcH7 expression and synphilin‐1 protein degradation in the mouse ventral midbrain

González-Barbosa

Mejía-García

Bautista

et al. 2017

J Biochem & Molecular Tox

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UbcH7 is an ubiquitin-conjugating enzyme that interacts with parkin, an E3 ligase. The UbcH7-parkin complex promotes the ubiquitination and degradation of several proteins via the 26S proteasome. Cellular accumulation of the UbcH7-parkin targets alpha-synuclein and synphilin-1 has been associated with Parkinson disease. In mouse liver, 2,3,7,8-tetrachlorodibenzo-p-dioxin, an aryl hydrocarbon receptor ligand, induces UbcH7 expression. Therefore, the aim of the present study was to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin induces Ubch7 mRNA and UbcH7 protein expression in the mouse brain, to characterize the molecular mechanism, and the effect on synphilin-1 half-life. We found that 2,3,7,8-tetrachlorodibenzo-p-dioxin promotes the aryl hydrocarbon receptor binding to Ubch7 gene promoter as well as its transactivation, resulting in an induction of UbcH7 levels in the olfactory bulb, ventral midbrain, hippocampus, striatum, cerebral cortex, brain stem, and medulla oblongata. In parallel, 2,3,7,8-tetrachlorodibenzo-p-dioxin promoted synphilin-1 degradation in an aryl hydrocarbon receptor-dependent way.

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Section: Methodsmentioning

confidence: 99%

“…Recently, we reported that induction of Ubch7 gene expression through the activation of the AHR results in ubiquitin proteasome system‐dependent p53 and c‐Fos degradation in mouse liver and Hepa‐1c1c7 cells . UBCH7 is a ubiquitin‐conjugating enzyme with the conserved catalytic domain UBC and is classified as an E2 class I enzyme .…”

Section: Introductionmentioning

confidence: 99%

TCDD induces UbcH7 expression and synphilin‐1 protein degradation in the mouse ventral midbrain

González-Barbosa

Mejía-García

Bautista

et al. 2017

J Biochem & Molecular Tox

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“…Ube2I expression is increased in response to 17β-estradiol under the control of the estrogen receptor (ERα) and nuclear factor Y 105 . Ube2L3 undergoes transcriptional regulation in response to aryl hydrocarbon receptor (AHR) signaling 106 . The resulting increase in Ube2L3 levels leads to degradation of cell cycle control proteins, identifying a connection between AHR signaling and the previously established role that Ube2L3 plays in cell cycle regulation 107 .…”

Section: Regulation Of E2 Activitymentioning

confidence: 99%

E2 enzymes: more than just middle men

et al. 2016

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Ubiquitin-conjugating enzymes (E2s) are the central players in the trio of enzymes responsible for the attachment of ubiquitin (Ub) to cellular proteins. Humans have ∼40 E2s that are involved in the transfer of Ub or Ub-like (Ubl) proteins (e.g., SUMO and NEDD8). Although the majority of E2s are only twice the size of Ub, this remarkable family of enzymes performs a variety of functional roles. In this review, we summarize common functional and structural features that define unifying themes among E2s and highlight emerging concepts in the mechanism and regulation of E2s.

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“…The aryl hydrocarbon receptor (AhR) mediates the expression of several genes encoding ubiquitin proteasome system proteins [14][15][16], in particular Ubch7 (also known as UBE2l3 in humans and UbcM4 in mice), an E2 ubiquitin enzyme partner of PRKN. AhR is a ligandactivated transcription factor that mediates the toxicity of environmental pollutants, and its highest-affinity ligand is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).…”

Section: Introductionmentioning

confidence: 99%

Parkin is transcriptionally regulated by the aryl hydrocarbon receptor: Impact on α-synuclein protein levels

González-Barbosa

García-Aguilar

Vega

et al. 2019

Biochemical Pharmacology

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Parkin (PRKN) is a ubiquitin E3 ligase that catalyzes the ubiquitination of several proteins. Mutations in the human Parkin gene, PRKN, leads to degeneration of dopaminergic (DA) neurons, resulting in autosomal recessive early-onset parkinsonism and the loss of PRKN function is linked to sporadic Parkinson's disease (PD). Additionally, several in vitro studies have shown that overexpression of exogenous PRKN protects against the neurotoxic effects induced by a wide range of cellular stressors, emphasizing the need to study the mechanism(s) governing PRKN expression and induction. Here, Prkn was identified as a novel target gene of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor and member of the bHLH/PAS (basic helixloop-helix/Per-Arnt-Sim) superfamily. AhR binds and transactivates the Prkn gene promoter. We also demonstrated that AhR is expressed in DA neurons and that its activation upregulates Prkn mRNA and protein levels in the mouse ventral midbrain. Additionally, the AhR-dependent increase in PRKN levels is associated with a decrease in the protein levels of its target substrate, α-synuclein, in an AhR-dependent manner, because this effect is not observed in Ahr-null mice. These results suggest that treatments designed to induce PRKN expression through the use of nontoxic AhR agonist ligands may be novel strategies to prevent and delay PD.

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Activation of AHR mediates the ubiquitination and proteasome degradation of c-Fos through the induction of Ubcm4 gene expression

Cited by 20 publications

References 44 publications

TCDD induces UbcH7 expression and synphilin‐1 protein degradation in the mouse ventral midbrain

TCDD induces UbcH7 expression and synphilin‐1 protein degradation in the mouse ventral midbrain

E2 enzymes: more than just middle men

Parkin is transcriptionally regulated by the aryl hydrocarbon receptor: Impact on α-synuclein protein levels

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