Discovery of a novel ligand that modulates the protein-protein
interactions of the AAA plus superfamily oncoprotein reptin

J 2015

Discovery of a novel ligand that modulates the protein-protein interactions of the AAA plus superfamily oncoprotein reptin

HEALY, AR, DR HOUSTON, L REMNANT, AS HUART, Veronika BRYCHTOVÁ et. al.

Základní údaje

Originální název

Discovery of a novel ligand that modulates the protein-protein interactions of the AAA plus superfamily oncoprotein reptin

Autoři

HEALY, AR, DR HOUSTON, L REMNANT, AS HUART, Veronika BRYCHTOVÁ, MM MASLON, O MEERS, Petr MÜLLER, Adam KREJČÍ, EA BLACKBURN, Bořivoj VOJTĚŠEK, L HERNYCHOVA, MD WALKINSHAW, NJ WESTWOOD a TR HUPP

Vydání

CHEMICAL SCIENCE, CAMBRIDGE, ROYAL SOC CHEMISTRY, 2015, 2041-6520

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.144

DOI

http://dx.doi.org/10.1039/c4sc03885a

UT WoS

000353223100055

Změněno: 10. 6. 2015 15:56, Mgr. Adam Krejčí, Ph.D.

Anotace

V originále

Developing approaches to discover protein-protein interactions (PPIs) remains a fundamental challenge. A chemical biology platform is applied here to identify novel PPIs for the AAA+ superfamily oncoprotein reptin. An in silico screen coupled with chemical optimization provided Liddean, a nucleotide-mimetic which modulates reptin's oligomerization status, protein-binding activity and global conformation. Combinatorial peptide phage library screening of Liddean-bound reptin with next generation sequencing identified interaction motifs including a novel reptin docking site on the p53 tumor suppressor protein. Proximity ligation assays demonstrated that endogenous reptin forms a predominantly cytoplasmic complex with its paralog pontin in cancer cells and Liddean promotes a shift of this complex to the nucleus. An emerging view of PPIs in higher eukaryotes is that they occur through a striking diversity of linear peptide motifs. The discovery of a compound that alters reptin's protein interaction landscape potentially leads to novel avenues for therapeutic development.

Citovat

HEALY, AR, DR HOUSTON, L REMNANT, AS HUART, Veronika BRYCHTOVÁ, MM MASLON, O MEERS, Petr MÜLLER, Adam KREJČÍ, EA BLACKBURN, Bořivoj VOJTĚŠEK, L HERNYCHOVA, MD WALKINSHAW, NJ WESTWOOD a TR HUPP. Discovery of a novel ligand that modulates the protein-protein interactions of the AAA plus superfamily oncoprotein reptin. CHEMICAL SCIENCE. CAMBRIDGE: ROYAL SOC CHEMISTRY, 2015, roč. 6, č. 5, s. 3109-3116. ISSN 2041-6520. Dostupné z: https://dx.doi.org/10.1039/c4sc03885a.

@article{1300730,
   author = {Healy, AR and Houston, DR and Remnant, L and Huart, AS and Brychtová, Veronika and Maslon, MM and Meers, O and Müller, Petr and Krejčí, Adam and Blackburn, EA and Vojtěšek, Bořivoj and Hernychova, L and Walkinshaw, MD and Westwood, NJ and Hupp, TR},
   article_location = {CAMBRIDGE},
   article_number = {5},
   doi = {http://dx.doi.org/10.1039/c4sc03885a},
   language = {eng},
   issn = {2041-6520},
   journal = {CHEMICAL SCIENCE},
   title = {Discovery of a novel ligand that modulates the protein-protein interactions of the AAA plus superfamily oncoprotein reptin},
   url = {http://dx.doi.org/10.1039/c4sc03885a},
   volume = {6},
   year = {2015}
}

TY  - JOUR
ID  - 1300730
AU  - Healy, AR - Houston, DR - Remnant, L - Huart, AS - Brychtová, Veronika - Maslon, MM - Meers, O - Müller, Petr - Krejčí, Adam - Blackburn, EA - Vojtěšek, Bořivoj - Hernychova, L - Walkinshaw, MD - Westwood, NJ - Hupp, TR
PY  - 2015
TI  - Discovery of a novel ligand that modulates the protein-protein interactions of the AAA plus superfamily oncoprotein reptin
JF  - CHEMICAL SCIENCE
VL  - 6
IS  - 5
SP  - 3109-3116
EP  - 3109-3116
PB  - ROYAL SOC CHEMISTRY
SN  - 20416520
UR  - http://dx.doi.org/10.1039/c4sc03885a
L2  - http://dx.doi.org/10.1039/c4sc03885a
N2  - Developing approaches to discover protein-protein interactions (PPIs) remains a fundamental challenge. A chemical biology platform is applied here to identify novel PPIs for the AAA+ superfamily oncoprotein reptin. An in silico screen coupled with chemical optimization provided Liddean, a nucleotide-mimetic which modulates reptin's oligomerization status, protein-binding activity and global conformation. Combinatorial peptide phage library screening of Liddean-bound reptin with next generation sequencing identified interaction motifs including a novel reptin docking site on the p53 tumor suppressor protein. Proximity ligation assays demonstrated that endogenous reptin forms a predominantly cytoplasmic complex with its paralog pontin in cancer cells and Liddean promotes a shift of this complex to the nucleus. An emerging view of PPIs in higher eukaryotes is that they occur through a striking diversity of linear peptide motifs. The discovery of a compound that alters reptin's protein interaction landscape potentially leads to novel avenues for therapeutic development.
ER  -

HEALY, AR, DR HOUSTON, L REMNANT, AS HUART, Veronika BRYCHTOVÁ, MM MASLON, O MEERS, Petr MÜLLER, Adam KREJČÍ, EA BLACKBURN, Bořivoj VOJTĚŠEK, L HERNYCHOVA, MD WALKINSHAW, NJ WESTWOOD a TR HUPP. Discovery of a novel ligand that modulates the protein-protein interactions of the AAA plus superfamily oncoprotein reptin. \textit{CHEMICAL SCIENCE}. CAMBRIDGE: ROYAL SOC CHEMISTRY, 2015, roč.~6, č.~5, s.~3109-3116. ISSN~2041-6520. Dostupné z: https://dx.doi.org/10.1039/c4sc03885a.

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