Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells

Kód výsledku v IS VaVaI

RIV/68378050:_____/12:00390227 - isvavai.cz

Výsledek na webu

http://dx.doi.org/10.1074/jbc.M111.316869

DOI - Digital Object Identifier

10.1074/jbc.M111.316869

Jazyk výsledku

angličtina

Název v původním jazyce

Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells

Popis výsledku v původním jazyce

Tumor suppressor PML is induced under viral and genotoxic stresses by interferons and JAK-STAT signaling. However, the mechanism responsible for its cell type-specific regulation under non-stimulated conditions is poorly understood. To analyze the variation of PML expression, we utilized three human cell types, BJ fibroblasts and HeLa and U2OS cell lines, each with a distinct PML expression pattern. Analysis of JAK-STAT signaling in the three cell lines revealed differences in levels of activated STAT3but not STAT1 correlating with PML mRNA and protein levels. RNAi-mediated knockdown of STAT3 decreased PML expression; both STAT3 level/activity and PML expression relied on IL6 secreted into culture media. We mapped the IL6-responsive sequence to an ISRE(-595/-628) element of the PML promoter. The PI3K/Akt/NF kappa B branch of IL6 signaling showed also cell-type dependence, being highest in BJ, intermediate in HeLa, and lowest in U2OS cells and correlated with IL6 secretion. RNAi-mediat

Název v anglickém jazyce

Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells

Popis výsledku anglicky

Tumor suppressor PML is induced under viral and genotoxic stresses by interferons and JAK-STAT signaling. However, the mechanism responsible for its cell type-specific regulation under non-stimulated conditions is poorly understood. To analyze the variation of PML expression, we utilized three human cell types, BJ fibroblasts and HeLa and U2OS cell lines, each with a distinct PML expression pattern. Analysis of JAK-STAT signaling in the three cell lines revealed differences in levels of activated STAT3but not STAT1 correlating with PML mRNA and protein levels. RNAi-mediated knockdown of STAT3 decreased PML expression; both STAT3 level/activity and PML expression relied on IL6 secreted into culture media. We mapped the IL6-responsive sequence to an ISRE(-595/-628) element of the PML promoter. The PI3K/Akt/NF kappa B branch of IL6 signaling showed also cell-type dependence, being highest in BJ, intermediate in HeLa, and lowest in U2OS cells and correlated with IL6 secretion. RNAi-mediat

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

GA204/08/1418: Úloha signalizační dráhy JAK/STAT v buněčné senescenci

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2012

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Svazek periodika

287

Číslo periodika v rámci svazku

32

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

26702-26714

Kód UT WoS článku

000307386000021

EID výsledku v databázi Scopus

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