Interplay between transcriptional and post-transcriptional regulation of Cyp2a5 expression

Glisovic, Tina; Söderberg, Malin; Christian, Kyle; Lang, Matti A.; Raffalli-Mathieu, Françoise

doi:10.1016/s0006-2952(03)00118-7

Cited by 17 publications

(21 citation statements)

References 35 publications

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“…Besides transcriptional regulation, CYP enzyme expression can be regulated at the post-transcriptional and post-translational levels through the interactions with 3'-UTR of their mRNAs by proteins such as the hnRNPA1 and micro RNA complexes (Glisovic et al, 2003;Christian et al, 2004;Tsuchiya et al, 2006), and by protein stabilisation (Abu-Bakar et al, 2012).…”

Section: Regulation Of Cyp Enzymesmentioning

confidence: 99%

“…The way in which the murine CYP2A5 is regulated during oxidative stress has been described extensively (Raffalli-Mathieu et al, 2002;Glisovic et al, 2003;Abu-Bakar et al, 2004;AbuBakar et al, 2005;Abu-Bakar et al, 2007;Kirby et al, 2011;Lamsa et al, 2012), but little is known about the mechanism(s) by which the human CYP2A6 is regulated under these conditions.…”

Section: Regulation Of Cyp Enzymesmentioning

confidence: 99%

“…Interestingly, hnRNPA1 a multifunctional stress activated gene regulator seems to contribute to strong and fast upregulation of the CYP2A5 during cellular stress (Glisovic et al, 2003). A recent study has also shown that the microRNA-126 binds to the 3'-UTR of CYP2A6 mRNA leading the translational repression of CYP2A6 expression (Nakano et al, 2015).…”

Section: Current Knowledge Of the Cyp2a6 Gene Regulatory Pathwaysmentioning

confidence: 99%

“…The hnRNPA1 is located in both cytosol and nucleus. However, certain form of stress such as transcription inhibition, inflammation or UV irritation, may cause its subcellular relocalisation (van der Houven van Oordt et al, 2000;Glisovic et al, 2003). The hnRNPA1 has been shown to bind to AG-rich motifs of the 3'UTR of HIV1, TAT and H-ras pre-mRNAs, exerting an essential role in the stabilisation of the RNAs (Damgaard et al, 2002;Guil et al, 2003).…”

Section: Post-transcriptional Regulation Of Cyp2a6 By Hnrnpa1mentioning

confidence: 99%

“…These stimuli include inflammatory cytokines, bacterial endotoxin, ultraviolet-A radiation, sodium arsenite, ethanol, and cadmium (Alam et al, 1989;Keyse and Tyrrell, 1989;Cantoni et al, 1991;Rizzardini et al, 1994;Gomes et al, 2010;Yeligar et al, 2010). Given that some of these agents are also known to induce CYP2A6 (Abu-Bakar et al, 2013) (Glisovic et al, 2003;AbuBakar et al, 2007;Arpiainen et al, 2007). Alterations in cellular redox state by chemicals activate these factors, leading in their translocation and accumulation in nucleus, where they bind to their respective response elements and drive the transcription of the Cyp2a5 gene.…”

Section: Bilirubin Oxidase As Part Of An Anti-oxidant Complex Againstmentioning

confidence: 99%

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Transcriptional regulation of human stress responsive cytochrome P450 2A6 (CYP2A6) by p53

Hu¹

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Human cytochrome P450 (CYP) 2A6 is highly expressed in the liver and the encoding gene is regulated by various stress activated transcription factors, such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf-2). Unlike the other xenobiotic metabolising CYP enzymes (XMEs), CYP2A6 only plays a minor role in xenobiotic metabolism. The CYP2A6 is highly induced by multiple forms of cellular stress conditions, where XMEs expression is normally inhibited. Recent findings suggest that the CYP2A6 plays an important role in regulating BR homeostasis.A computer based sequence analysis on the 3 kb proximate CYP2A6 promoter revealed several putative binding sites for p53, a protein that mediates regulation of antioxidant and apoptosis pathways. In this study, the role of p53 in CYP2A6 gene regulation is demonstrated.The site closest to transcription start site (TSS) is highly homologous with the p53 consensus Replacing the p53RE on the proximal CYP2A6 promoter with a consensus p53RE resulted in an extremely high expression of the recombinant gene regardless of p53 overexpression.While unexpected, this result agrees with the rest of the evidence and supports a model where the stress activated proteins form a compact cluster, assisted by the liver specific HNF-4a for full activity.It has been shown that p53 interacts with Nrf-2 exerting a role in regulating several stress activated genes. Co-transfection of Nrf-2 and p53 together with CYP2A6 promoter in C3A cells demonstrated that the Nrf-2 restrained the p53-mediated CYP2A6 transactivation probably through the "stress cluster" present on the promoter region. Stepwise truncations of the distal CYP2A6 promoter followed by transfection of these promoters into the C3A cells also suggested that the potential suppressor(s) may exist on the "-2253 to -1700bp" and "-688 to-250bp" regions of the promoter.Collectively, the results provide a mechanistic explanation for previous observations that the CYP2A6 is induced by various structurally unrelated toxic insults.ii

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Section: Regulation Of Cyp Enzymesmentioning

confidence: 99%

Section: Regulation Of Cyp Enzymesmentioning

confidence: 99%

Section: Current Knowledge Of the Cyp2a6 Gene Regulatory Pathwaysmentioning

confidence: 99%

Section: Post-transcriptional Regulation Of Cyp2a6 By Hnrnpa1mentioning

confidence: 99%

Section: Bilirubin Oxidase As Part Of An Anti-oxidant Complex Againstmentioning

confidence: 99%

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Transcriptional regulation of human stress responsive cytochrome P450 2A6 (CYP2A6) by p53

Hu¹

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Glutamine increases stability of TPH1 mRNA via p38 mitogen-activated kinase in mouse mastocytoma cells

et al. 2022

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Expression changes for tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, by environmental glutamine (GLN) were examined in mouse mastocytoma-derived P815-HTR cells. GLN-treated cells exhibited a robust increase in TPH1 mRNA after a 6 h exposure to GLN. 6-Diazo-5-oxo-L-norleucine (DON), a glutamine-utilizing glutaminase inhibitor, significantly inhibited the GLN-induction of TPH1 mRNA. Nuclear run-on assays and mRNA decay experiments demonstrated that the primary mechanism leading to increased TPH1 mRNA levels was not due to transcriptional changes, but rather due to increased TPH1 RNA stability induced by GLN. Treatment with GLN also led to activation of p38 MAP kinase, but not p42/44 MAPK. In addition, SB203580, a p38 MAP kinase specific inhibitor, completely abolished the GLN-mediated increase of TPH1 mRNA levels, suggesting the pathway stabilizing TPH1 mRNA might be mediated by the activated p38 MAP kinase pathway. Additionally, SB203580 significantly reduced the stability of TPH1 mRNA, and this reduction of the stability was not affected by GLN in the culture medium, implying a sequential signaling from GLN being mediated by p38 MAP kinase, resulting in alteration of TPH1 mRNA stability. TPH1 mRNA stability loss was also dependent on de novo protein synthesis as shown by treatment of cells with a transcriptional/translational blocker. We provide evidence that TPH1 mRNA levels are increased in response to increased exogenous GLN in mouse mastocytoma cells via a stabilization of TPH1 mRNA due to the activity of the p38 MAP kinase.

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Enzyme Regulation*

Ding

Zhang

2010

Comprehensive Toxicology

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Interplay between transcriptional and post-transcriptional regulation of Cyp2a5 expression

Cited by 17 publications

References 35 publications

Transcriptional regulation of human stress responsive cytochrome P450 2A6 (CYP2A6) by p53

Transcriptional regulation of human stress responsive cytochrome P450 2A6 (CYP2A6) by p53

Glutamine increases stability of TPH1 mRNA via p38 mitogen-activated kinase in mouse mastocytoma cells

Enzyme Regulation*

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