A novel p53 phosphorylation site within the MDM2 ubiquitination signal: I. phosphorylation at SER269 in vivo is linked to inactivation of p53 function

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F10%3A%230000122" target="_blank" >RIV/00209805:_____/10:#0000122 - 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

A novel p53 phosphorylation site within the MDM2 ubiquitination signal: I. phosphorylation at SER269 in vivo is linked to inactivation of p53 function

Popis výsledku v původním jazyce

p53 is a thermodynamically unstable protein containing a conformationally flexible multiprotein docking site within the DNA-binding domain. A combinatorial peptide chip used to identify the novel kinase consensus site RXS?(K/D) led to the discovery of ahomologous phosphorylation site in the S10 ?-strand of p53 at Ser(269). Mutation or phosphorylation of p53 at Ser(269) attenuates binding of the p53-specific monoclonal antibody DO-12. Phospho-Ser(269)-specific monoclonal antibodies were generated and used to demonstrate that p53 phosphorylation is induced at Ser(269) after irradiation with kinetics similar to those of p53 protein induction. Phosphomimetic mutation at Ser(269) inactivated the transcription activation function and clonogenic suppressor activity of p53. These data suggest that the dynamic equilibrium between native and unfolded states of WT p53 can be modulated by phosphorylation of the conformationally flexible multiprotein binding site in the p53 DNA-binding domain.

Název v anglickém jazyce

A novel p53 phosphorylation site within the MDM2 ubiquitination signal: I. phosphorylation at SER269 in vivo is linked to inactivation of p53 function

Popis výsledku anglicky

p53 is a thermodynamically unstable protein containing a conformationally flexible multiprotein docking site within the DNA-binding domain. A combinatorial peptide chip used to identify the novel kinase consensus site RXS?(K/D) led to the discovery of ahomologous phosphorylation site in the S10 ?-strand of p53 at Ser(269). Mutation or phosphorylation of p53 at Ser(269) attenuates binding of the p53-specific monoclonal antibody DO-12. Phospho-Ser(269)-specific monoclonal antibodies were generated and used to demonstrate that p53 phosphorylation is induced at Ser(269) after irradiation with kinetics similar to those of p53 protein induction. Phosphomimetic mutation at Ser(269) inactivated the transcription activation function and clonogenic suppressor activity of p53. These data suggest that the dynamic equilibrium between native and unfolded states of WT p53 can be modulated by phosphorylation of the conformationally flexible multiprotein binding site in the p53 DNA-binding domain.

Druh

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

CEP obor

FD - Onkologie a hematologie

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)

Rok uplatnění

2010

Kód důvěrnosti údajů

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

Název periodika

The Journal of biological chemistry

ISSN

0021-9258

e-ISSN

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Svazek periodika

285

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

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Kód UT WoS článku

000284424000068

EID výsledku v databázi Scopus

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