Protein-protein interactions modulate the docking­dependent E3-ubiquitin ligase activity of CHIP

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F15%3A%230000648" target="_blank" >RIV/00209805:_____/15:#0000648 - isvavai.cz</a>

Result on the web

<a href="http://www.mcponline.org/content/14/11/2973.long" target="_blank" >http://www.mcponline.org/content/14/11/2973.long</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/mcp.M115.051169" target="_blank" >10.1074/mcp.M115.051169</a>

Result language

angličtina

Original language name

Protein-protein interactions modulate the docking­dependent E3-ubiquitin ligase activity of CHIP

Original language description

CHIP is a tetratricopeptide repeat (TPR) domain protein that functions as an E3-ubiquitin ligase. As well as linking the molecular chaperones to the ubiquitin proteasome system, CHIP also has a docking-dependent mode where it ubiquitinates native substrates, thereby regulating their steady state levels and/or function. Here we explore the effect of Hsp70 on the docking-dependent E3-ligase activity of CHIP. The TPR-domain is revealed as a binding site for allosteric modulators involved in determining CHIP's dynamic conformation and activity. Biochemical, biophysical and modeling evidence demonstrate that Hsp70-binding to the TPR, or Hsp70-mimetic mutations, regulate CHIP-mediated ubiquitination of p53 and IRF-1 through effects on U-box activity and substrate binding. HDX-MS was used to establish that conformational-inhibition-signals extended from the TPR-domain to the U-box. This underscores inter-domain allosteric regulation of CHIP by the core molecular chaperones. Defining the chape

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2015

Confidentiality

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

Name of the periodical

Molecular and cellular proteomics

ISSN

1535-9476

e-ISSN

—

Volume of the periodical

14

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

6

Pages from-to

2973-2978

UT code for WoS article

000365636800011

EID of the result in the Scopus database

2-s2.0-84946098298