Grégory Chevillard

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PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift...

NFE2L3 [Nuclear factor (erythroid-derived 2)-like 3] or NRF3, a member of the Cap'n'Collar (CNC) family, is a basic-region leucine zipper (bZIP) transcription factor that was first identified over 10 years ago. Contrary to its extensively studied homolog NFE2L2 (NRF2), the regulation and function of the NFE2L3 protein have not yet attracted as much...

We have previously generated mice deficient for Nfe213 (NF-E2 p45 related factor 3 or Nrf3), a member of the cap 'n' collar family of basic-leucine zipper transcription factors. To examine whether Nrf3 is involved in chemical-induced carcinogenesis, we exposed the mice to benzo[a]pyrene (B[a]P), a carcinogen found in cigarette smoke. Contrary to wi...

Peroxisomal 3-ketoacyl-CoA thiolase B (Thb) catalyzes the final step in the peroxisomal β-oxidation of straight-chain acyl-CoAs and is under the transcription control of the nuclear hormone receptor PPARα. PPARα binds to and is activated by the synthetic compound Wy14,643 (Wy). Here, we show that the magnitude of Wy-mediated induction of peroxisoma...

PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift...

We found that both wild type and Nrf3 (NF-E2-related factor 3) deficient mice are sensitive to BHT single administration exhibiting respiratory distress and considerably lose body weight following treatment. At time of sacrifice, the BHT-treated Nrf3-/- mice had lost significantly more body weight than their WT counterparts. In the lung, transcript...

In this study, we investigated the role of the transcription factor Nrf3 in chemical carcinogenesis induced by benzo[a]pyrene, a common carcinogen found in cigarette smoke, car exhaust and charcoal-grilled meats. Wild type and Nrf3-deficient mice were treated weekly for 4 consecutive weeks with benzo[a]pyrene and then sacrificed 30 weeks after the...

1988 Poster Board I-1010 The NF-E2 transcription factor is a heterodimer composed of a large hematopoietic-specific subunit called p45 and widely expressed 18 to 20-kDa small Maf subunits. In MEL (mouse erythroleukemia) cells, a model of erythroid differentiatin, the absence of p45 is inhibiting chemically induced differentiation, including inducti...

The peroxisomal 3-ketoacyl-CoA thiolase B (Thb) gene was previously identified as a direct target gene of PPARalpha, a nuclear hormone receptor activated by hypolipidemic fibrate drugs. To better understand the role of ThB in hepatic lipid metabolism in mice, Sv129 wild-type and Thb null mice were fed or not the selective PPARalpha agonist Wy14,643...

We analyzed the response of uterine smooth muscle cells to interleukin-1beta (IL-1beta). We first showed that PHM1-31 myometrial cells, our cellular model, are contractile. To determine the molecular mechanisms of uterine smooth muscle cell activation by proinflammatory cytokines, we performed genechip expression array profiling studies of PHM1-31...

We have analysed the molecular and cellular regulation of the basic-leucine zipper (bZIP) transcription factor Nrf3 (NFE2-Related Factor 3). Cycloheximide studies revealed a rapid turnover of Nrf3. We showed that the proteasome inhibitor MG-132 increases Nrf3 protein levels. Furthermore, we demonstrated that Nrf3 is an N-glycosylated protein associ...

The peroxisomal beta-oxidation system consists of four steps catalysed by three enzymes: acyl-CoA oxidase, 3-hydroxyacyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase. In humans, thiolase activity is encoded by one gene, whereas in rodents, three enzymes encoded by three distinct genes (i.e. thiolase A, thiolas...

Peroxisome proliferator-activated receptor alpha (PPARalpha) activation by fibrates controls expression of several genes involved in hepatic cholesterol metabolism. Other genes could be indirectly controlled in response to changes in cellular cholesterol availability. To further understand how fibrates may affect cholesterol synthesis, we investiga...

In rats, two peroxisomal 3-ketoacyl-CoA thiolase genes (A and B) have been cloned, whereas only one thiolase gene is found in humans. The aim of this study was thus to clone the different mouse thiolase genes in order to study both their tissue expression and their associated enzymatic activity. In this study, we cloned and characterized two mouse...

Our laboratory cloned two peroxisomal 3-ketoacyl-CoA thiolase genes in mouse. These genes were named mThA (mouse peroxisomal Thiolase A) and mThB (mouse peroxisomal Thiolase B) by comparison with peroxisomal thiolase genes known in rat (Hijikata et al. 1990, Bodnar & Rachubinski, 1990). In this study, we analysed the tissue expression of the two th...

Many peroxisomal enzymes are controlled at the transcriptional level. This gene regulation is well documented in liver from rodent species and is more important upon peroxisome proliferation, although both phenomena are not always associated. Understanding of this regulation comes largely from studies on PPARs (Peroxisome Proliferator-Activated Rec...

Anaplastic large cell lymphomas (ALCLs) are frequently associated with the t(2;5)(p23;q35) translocation, leading to the expression of NPM-ALK, a fusion protein linking nucleophosmin and anaplastic lymphoma kinase, a receptor tyrosine kinase. In ALCLs, dimerization of NPM-ALK leads to constitutive autophosphorylation and activation of the kinase, n...