Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F10%3A00347137" target="_blank" >RIV/68378050:_____/10:00347137 - 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

Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling

Popis výsledku v původním jazyce

PML tumor suppressor is upregulated in several forms of cellular senescence, however the mechanism of its induction is elusive. Here we show that genotoxic drugs that induce senescence, such as bromodeoxyuridine, thymidine, distamycin A, aphidicolin, etoposide and camptothecin evoke expansion of PML nuclear compartment and its association with persistent DNA lesions in several human normal and cancer cells. This phenomenon was accompanied by elevation of PML transcripts. Chemical inhibition of all JAK kinases and RNAi-mediated knock-down of JAK1 suppressed PML expression, implicating JAK/STAT-mediated signaling in regulation of the PML gene. Our data show that upregulation of the PML tumor suppressor in cellular senescence triggered by diverse drugs including clinically used anti-cancer chemotherapeutics relies on stimulation of PML transcription by JAK/STAT-mediated signaling, possibly evoked by the autocrine/paracrine activities of senescence-associated cytokines.

Název v anglickém jazyce

Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling

Popis výsledku anglicky

PML tumor suppressor is upregulated in several forms of cellular senescence, however the mechanism of its induction is elusive. Here we show that genotoxic drugs that induce senescence, such as bromodeoxyuridine, thymidine, distamycin A, aphidicolin, etoposide and camptothecin evoke expansion of PML nuclear compartment and its association with persistent DNA lesions in several human normal and cancer cells. This phenomenon was accompanied by elevation of PML transcripts. Chemical inhibition of all JAK kinases and RNAi-mediated knock-down of JAK1 suppressed PML expression, implicating JAK/STAT-mediated signaling in regulation of the PML gene. Our data show that upregulation of the PML tumor suppressor in cellular senescence triggered by diverse drugs including clinically used anti-cancer chemotherapeutics relies on stimulation of PML transcription by JAK/STAT-mediated signaling, possibly evoked by the autocrine/paracrine activities of senescence-associated cytokines.

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

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2010

Kód důvěrnosti údajů

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

Název periodika

Cell Cycle

ISSN

1538-4101

e-ISSN

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Svazek periodika

9

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

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Kód UT WoS článku

000281206300038

EID výsledku v databázi Scopus

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