Colorectal cancer specific cytochrome P450 2W1 (CYP2W1): intracellular localization, glycosylation, and catalytic activity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F10%3A10080527" target="_blank" >RIV/00179906:_____/10:10080527 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Colorectal cancer specific cytochrome P450 2W1 (CYP2W1): intracellular localization, glycosylation, and catalytic activity

Popis výsledku v původním jazyce

Cytochrome P450 2W1 (CYP2W1) is expressed at high levels in colorectal cancer cells. We have shown previously that a higher tumor expression is associated with less survival. In this study, we characterize post-translational modification, inverted endoplasmic reticulum (ER) topology, and catalytic activity of CYP2W1. Immunofluorescence microscopy and cell surface biotinylation experiments revealed approx. 8% of the CYP2W1 on the cell surface. Despite the reverse orientation of CYP2W1 in the ER membrane,apparently making interactions with NADPH-cytochrome P450 reductase impossible, CYP2W1 in HEK293 cells was active in the metabolism of indoline substrates and in activation of aflatoxin B1 into cytotoxic products. The study identifies for the first timea cytochrome P450 with a luminal ER orientation and still retaining catalytic activity. The results suggest a possibility of using CYP2W1 as a drug target in the treatment of colon cancer using antibodies and/or specific CYP2W1 activated

Název v anglickém jazyce

Colorectal cancer specific cytochrome P450 2W1 (CYP2W1): intracellular localization, glycosylation, and catalytic activity

Popis výsledku anglicky

Cytochrome P450 2W1 (CYP2W1) is expressed at high levels in colorectal cancer cells. We have shown previously that a higher tumor expression is associated with less survival. In this study, we characterize post-translational modification, inverted endoplasmic reticulum (ER) topology, and catalytic activity of CYP2W1. Immunofluorescence microscopy and cell surface biotinylation experiments revealed approx. 8% of the CYP2W1 on the cell surface. Despite the reverse orientation of CYP2W1 in the ER membrane,apparently making interactions with NADPH-cytochrome P450 reductase impossible, CYP2W1 in HEK293 cells was active in the metabolism of indoline substrates and in activation of aflatoxin B1 into cytotoxic products. The study identifies for the first timea cytochrome P450 with a luminal ER orientation and still retaining catalytic activity. The results suggest a possibility of using CYP2W1 as a drug target in the treatment of colon cancer using antibodies and/or specific CYP2W1 activated

Druh

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

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

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Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2010

Kód důvěrnosti údajů

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

Název periodika

Molecular Pharmacology

ISSN

0026-895X

e-ISSN

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Svazek periodika

78

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

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Kód UT WoS článku

000284267200004

EID výsledku v databázi Scopus

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