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

Result code in 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>

Alternative codes found

RIV/00216208:11160/13:10146001

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

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Project

<a href="/en/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centre of drug-dietary supplements interactions and nutrigenetics</a><br>

Continuities

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

Publication year

2013

Confidentiality

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

Name of the periodical

Archives of Toxicology

ISSN

0340-5761

e-ISSN

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Volume of the periodical

87

Issue of the periodical within the volume

2

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

291-301

UT code for WoS article

000314023900007

EID of the result in the Scopus database

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