Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels
independent of its deubiquitinase activity

J 2017

Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity

CETKOVSKÁ, Kateřina, Hana ŠUSTOVÁ a Stjepan ULDRIJAN

Základní údaje

Originální název

Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity

Autoři

CETKOVSKÁ, Kateřina (203 Česká republika, domácí), Hana ŠUSTOVÁ (203 Česká republika, domácí) a Stjepan ULDRIJAN (203 Česká republika, garant, domácí)

Vydání

Scientific Reports, LONDON, NATURE PUBLISHING GROUP, 2017, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.122

Kód RIV

RIV/00216224:14110/17:00094686

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1038/srep43180

UT WoS

000394930100001

Klíčová slova anglicky

Mdm2

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 3. 2018 16:41, Soňa Böhmová

Anotace

V originále

The overexpression of Mdm2 has been linked to the loss of p53 tumour suppressor activity in several human cancers. Here, we present results suggesting that ubiquitin-specific peptidase 48 (USP48), a deubiquitinase that has been linked in previous reports to the NF-kappa B signaling pathway, is a novel Mdm2 binding partner that promotes Mdm2 stability and enhances Mdm2-mediated p53 ubiquitination and degradation. In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels. Moreover, two previously characterized USP48 mutants lacking deubiquitinase activity were also capable of efficiently stabilizing Mdm2, indicating that USP48 utilizes a non-canonical, deubiquitination-independent mechanism to promote Mdm2 oncoprotein stability. This study represents, to the best of our knowledge, the first report suggesting DUB-mediated target protein stabilization that is independent of its deubiquitinase activity. In addition, our results suggest that USP48 might represent a new mechanism of crosstalk between the NF-kappa B and p53 stress response pathways.

Návaznosti

GA14-12166S, projekt VaV

Název: Regulace dráhy nádorového supresoru p53 novými vazebnými partnery onkogenů Mdm2 a Mdm4

Investor: Grantová agentura ČR, Regulace dráhy nádorového supresoru p53 novými vazebnými partnery onkogenů Mdm2 a Mdm4

MUNI/A/1171/2015, interní kód MU

Název: Molekulárně buněčná biologie pro biomedicínu

Investor: Masarykova univerzita, Molekulárně buněčná biologie pro biomedicínu, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

CETKOVSKÁ, Kateřina, Hana ŠUSTOVÁ a Stjepan ULDRIJAN. Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity. Scientific Reports. LONDON: NATURE PUBLISHING GROUP, 2017, roč. 7, FEB 24 2017, s. 1-9. ISSN 2045-2322. Dostupné z: https://dx.doi.org/10.1038/srep43180.

@article{1376239,
   author = {Cetkovská, Kateřina and Šustová, Hana and Uldrijan, Stjepan},
   article_location = {LONDON},
   article_number = {FEB 24 2017},
   doi = {http://dx.doi.org/10.1038/srep43180},
   keywords = {Mdm2},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific Reports},
   title = {Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity},
   volume = {7},
   year = {2017}
}

TY  - JOUR
ID  - 1376239
AU  - Cetkovská, Kateřina - Šustová, Hana - Uldrijan, Stjepan
PY  - 2017
TI  - Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity
JF  - Scientific Reports
VL  - 7
IS  - FEB 24 2017
SP  - 1-9
EP  - 1-9
PB  - NATURE PUBLISHING GROUP
SN  - 20452322
KW  - Mdm2
N2  - The overexpression of Mdm2 has been linked to the loss of p53 tumour suppressor activity in several human cancers. Here, we present results suggesting that ubiquitin-specific peptidase 48 (USP48), a deubiquitinase that has been linked in previous reports to the NF-kappa B signaling pathway, is a novel Mdm2 binding partner that promotes Mdm2 stability and enhances Mdm2-mediated p53 ubiquitination and degradation. In contrast to other deubiquitinating enzymes (DUBs) that have been previously implicated in the regulation of Mdm2 protein stability, USP48 did not induce Mdm2 stabilization by significantly reducing Mdm2 ubiquitination levels. Moreover, two previously characterized USP48 mutants lacking deubiquitinase activity were also capable of efficiently stabilizing Mdm2, indicating that USP48 utilizes a non-canonical, deubiquitination-independent mechanism to promote Mdm2 oncoprotein stability. This study represents, to the best of our knowledge, the first report suggesting DUB-mediated target protein stabilization that is independent of its deubiquitinase activity. In addition, our results suggest that USP48 might represent a new mechanism of crosstalk between the NF-kappa B and p53 stress response pathways.
ER  -

CETKOVSKÁ, Kateřina, Hana ŠUSTOVÁ a Stjepan ULDRIJAN. Ubiquitin-specific peptidase 48 regulates Mdm2 protein levels independent of its deubiquitinase activity. \textit{Scientific Reports}. LONDON: NATURE PUBLISHING GROUP, 2017, roč.~7, FEB 24 2017, s.~1-9. ISSN~2045-2322. Dostupné z: https://dx.doi.org/10.1038/srep43180.

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