AML-related NPM mutations drive p53 delocalization into the cytoplasm with possible impact on p53-dependent stress response

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023736%3A_____%2F21%3A00013253" target="_blank" >RIV/00023736:_____/21:00013253 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11320/21:10434474

Výsledek na webu

<a href="https://doi.org/10.3390/cancers13133266" target="_blank" >https://doi.org/10.3390/cancers13133266</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cancers13133266" target="_blank" >10.3390/cancers13133266</a>

Jazyk výsledku

angličtina

Název v původním jazyce

AML-related NPM mutations drive p53 delocalization into the cytoplasm with possible impact on p53-dependent stress response

Popis výsledku v původním jazyce

We investigated p53-NPM interaction in live HEK-293T cells by FLIM-FRET and in cell lysates by immunoprecipitation. eGFP lifetime-photoconversion was used to follow redistribution dynamics of NPMmut and p53 in Selinexor-treated cells. We confirmed the p53-NPMwt interaction in intact cells and newly documented that this interaction is not compromised by the NPM mutation causing displacement of p53 to the cytoplasm. Moreover, the interaction was not abolished for non-oligomerizing NPM variants with truncated oligomerization domain, suggesting that oligomeriza-tion is not essential for interaction of NPM forms with p53. Inhibition of the nuclear exporter XPO1 by Selinexor caused expected nuclear relocalization of both NPMmut and p53. However, significantly different return rates of these proteins indicate nontrivial mechanism of p53 and NPMmut cellular trafficking. The altered p53 regulation in cells expressing NPMmut offers improved understanding to help investigational strategies targeting these mutations.

Název v anglickém jazyce

AML-related NPM mutations drive p53 delocalization into the cytoplasm with possible impact on p53-dependent stress response

Popis výsledku anglicky

We investigated p53-NPM interaction in live HEK-293T cells by FLIM-FRET and in cell lysates by immunoprecipitation. eGFP lifetime-photoconversion was used to follow redistribution dynamics of NPMmut and p53 in Selinexor-treated cells. We confirmed the p53-NPMwt interaction in intact cells and newly documented that this interaction is not compromised by the NPM mutation causing displacement of p53 to the cytoplasm. Moreover, the interaction was not abolished for non-oligomerizing NPM variants with truncated oligomerization domain, suggesting that oligomeriza-tion is not essential for interaction of NPM forms with p53. Inhibition of the nuclear exporter XPO1 by Selinexor caused expected nuclear relocalization of both NPMmut and p53. However, significantly different return rates of these proteins indicate nontrivial mechanism of p53 and NPMmut cellular trafficking. The altered p53 regulation in cells expressing NPMmut offers improved understanding to help investigational strategies targeting these mutations.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

<a href="/cs/project/GA19-04099S" target="_blank" >GA19-04099S: Role interakční sítě nukleofosminu v akutní myeloidní leukémii s mutovaným NPM</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Cancers

ISSN

2072-6694

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

13

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

24

Strana od-do

"art. no. 3266"

Kód UT WoS článku

000671357300001

EID výsledku v databázi Scopus

2-s2.0-85108738984