The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation

Pollenz, Richard S.

doi:10.1016/s0009-2797(02)00065-0

Cited by 211 publications

(159 citation statements)

References 67 publications

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“…It has recently been demonstrated that inhibition of proteosomal degradation enhances the transcriptional response mediated by some nuclear receptors (Blanquart et al, 2002;Deroo et al, 2002;Pollenz, 2002) and the Ets protein E1AF (Takahashi et al, 2005). We show here that blocking protein turnover with the proteasome inhibitor ALLN or MG132 also induces a change in ERM transcriptional activity.…”

Section: Discussionsupporting

confidence: 53%

The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity

et al. 2006

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ERM is a member of the ETS transcription factor family. High levels of the corresponding mRNA are detected in a variety of human breast cancer cell lines, as well as in aggressive human breast tumors. As ERM protein is almost undetectable in these cells, high degradation of this transcription factor has been postulated. Here we have investigated whether ERM degradation might depend on the proteasome pathway. We show that endogenous and ectopically expressed ERM protein is short-lived protein and undergoes proteasome-dependent degradation. Deletion mutagenesis studies indicate that the 61 C-terminal amino acids of ERM are critical for its proteolysis and serve as a degradation signal. Although ERM conjugates with ubiquitin, this post-translational modification does not depend on the C-terminal domain. We have used an Ets-responsive ICAM-1 reporter plasmid to show that the ubiquitin-proteasome pathway can affect transcriptional function of ERM. Thus, ERM is subject to degradation via the 26S proteasome pathway, and this pathway probably plays an important role in regulating ERM transcriptional activity.

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Section: Discussionsupporting

confidence: 53%

The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity

et al. 2006

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“…However, CYP1A1 only correlated with cytosolic AhR. It is well known that AhR is constitutively expressed in the cytosol of cultivated epithelial cells and is transiently translocated into the nucleus following treatment with ligands, where it interacts with dioxin response element (DRE) and then returns to the cytosol (Pollenz, 2002). Therefore, it is reasonable that elevated AhR expression in the cytosol of tumor cells is significantly correlated with CYP1A1 expression in ever smokers who have been exposed to exogenous AhR ligands from cigarette smoke.…”

Section: Resultsmentioning

confidence: 99%

Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer

Chang

et al. 2011

Oncogene

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“…Up-regulation of a receptor's presence increases the potency of its ligand and is referred to as "sensitization", while down regulation results in "desensitization" and subsequent tolerance. In such a manner, AHR expression is significantly influenced by dose and duration of TCDD exposure (Pollenz, 2002). Following short-term in vitro exposure of cultured Hepa-1 cells to 2 nM TCDD, AHR levels are reduced to less than 20% of original levels within 6 hours following treatment, and this desensitization persists for at least 72 hours (Giannone et al, 1998).…”

Section: Principles Of Tcdd Sensitivitymentioning

confidence: 99%

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

et al. 2005

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ᮀTCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic in either bacteria or most in vitro assay systems. They do so in spite of having repeatedly been linked to oxidative stress and to mutagenic and carcinogenic outcomes. Oxidative stress, on the other hand, has been used as a marker for the toxicity of dioxin and its congeners. We have focused this review on the connection between oxidative stress induction and the toxic effects of fetal and adult dioxin exposure, with emphasis on the large species difference in sensitivity to this agent. We examine the roles that the dioxin-inducible cytochromes P450s play in the cellular and toxicological consequences of dioxin exposure with emphasis on oxidative stress involvement. Many components of the health consequences resulting from dioxin exposure may be attributable to epigenetic mechanisms arising from prolonged reactive oxygen generation.

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The mechanism of AH receptor protein down-regulation (degradation) and its impact on AH receptor-mediated gene regulation

Cited by 211 publications

References 67 publications

The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity

The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity

Aryl hydrocarbon receptor in association with RelA modulates IL-6 expression in non-smoking lung cancer

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

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