The role of residues T248, Y249 and T422 in the function of human pregnane X receptor

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F13%3A33147431" target="_blank" >RIV/61989592:15310/13:33147431 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/13:10146001

Výsledek na webu

<a href="http://link.springer.com/article/10.1007%2Fs00204-012-0937-9" target="_blank" >http://link.springer.com/article/10.1007%2Fs00204-012-0937-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-012-0937-9" target="_blank" >10.1007/s00204-012-0937-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The role of residues T248, Y249 and T422 in the function of human pregnane X receptor

Popis výsledku v původním jazyce

The pregnane X receptor (PXR) is a key xenobiotic receptor that regulates the expression of numerous drug-metabolizing enzymes. Some posttranslational mechanisms modulate its transcriptional activity. Although several kinases have been shown to directlyphosphorylate this receptor, little is known about phosphorylation sites of PXR. In the present work, we examined T248, Y249 and T422 putative phosphorylation sites determined based on in silico consensus kinase site prediction analysis. T248 and T422 residues are critical for the interaction of the PXR ligand-binding domain and the activation function-2 (AF2) domain. Site-directed mutagenesis analysis was performed to generate phospho-deficient and phospho-mimetic mutants. We examined transactivation activity of the PXR mutants in gene reporter assays, formation of PXRmutant/RXRalfa heterodimer, binding of PXR mutants to the CYP3A4 gene response element DR3 and CYP3A4 expression in HepG2 cells after expression of the mutants. We found

Název v anglickém jazyce

The role of residues T248, Y249 and T422 in the function of human pregnane X receptor

Popis výsledku anglicky

The pregnane X receptor (PXR) is a key xenobiotic receptor that regulates the expression of numerous drug-metabolizing enzymes. Some posttranslational mechanisms modulate its transcriptional activity. Although several kinases have been shown to directlyphosphorylate this receptor, little is known about phosphorylation sites of PXR. In the present work, we examined T248, Y249 and T422 putative phosphorylation sites determined based on in silico consensus kinase site prediction analysis. T248 and T422 residues are critical for the interaction of the PXR ligand-binding domain and the activation function-2 (AF2) domain. Site-directed mutagenesis analysis was performed to generate phospho-deficient and phospho-mimetic mutants. We examined transactivation activity of the PXR mutants in gene reporter assays, formation of PXRmutant/RXRalfa heterodimer, binding of PXR mutants to the CYP3A4 gene response element DR3 and CYP3A4 expression in HepG2 cells after expression of the mutants. We found

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centrum interakcí potravních doplňků s léčivy a nutrigenetiky</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Archives of Toxicology

ISSN

0340-5761

e-ISSN

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Svazek periodika

87

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

291-301

Kód UT WoS článku

000314023900007

EID výsledku v databázi Scopus

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