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MisloQC SIGNED

Dissecting Quality Control Mechanisms of Mislocalized Proteins

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EC-Contrib. €

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Project "MisloQC" data sheet

The following table provides information about the project.

Coordinator
INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH 

Organization address
address: ACKERMANNWEG 4
city: MAINZ
postcode: 55128
website: www.imb-mainz.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙497˙750 €
 EC max contribution 1˙497˙750 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2023-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH DE (MAINZ) coordinator 1˙497˙750.00

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 Project objective

Protein quality control systems maintain a functional proteome through detection and removal of abnormal proteins. While typically only misfolded or damaged molecules are thought of as abnormal, recent work has revealed that also mislocalized proteins are subject to quality control. Mislocalized proteins are defined as proteins that fail to reach their native compartment or fail to assemble into their native complex, and thus cannot function normally. Protein mislocalization is a constitutive problem caused by inefficiencies of cellular processes and increases with aging. Proteins can also mislocalize due to mutations, as seen in various metabolic, cardiovascular and neurodegenerative diseases, and some types of cancer. Despite the ubiquity of protein mislocalization, the systems performing quality control of mislocalized proteins are unknown for most of the proteome because quality control substrates are usually rare, thus difficult to identify, and there is considerable redundancy built into quality control systems. Here, I propose to systematically dissect quality control mechanisms of mislocalized proteins through a combination of molecular biology, genetics, biochemistry and computational biology in yeast and human cells. We will establish a platform for conditional protein mislocalization and apply it (i) to identify quality control substrates proteome-wide, (ii) to dissect redundancies in quality control systems, (iii) to identify the machinery responsible for quality control of mislocalized proteins and (iv) to map the features involved in substrate recognition by the quality control machinery. Finally, we will exploit our findings to selectively target aneuploid cancer cells, which exhibit a high burden of mislocalized proteins. This work will provide a comprehensive picture of quality control systems for mislocalized proteins and shed light on their roles under both normal and perturbed conditions.

 Publications

year authors and title journal last update
List of publications.
2019 Verena Dederer, Anton Khmelinskii, Anna Gesine Huhn, Voytek Okreglak, Michael Knop, Marius K Lemberg
Cooperation of mitochondrial and ER factors in quality control of tail-anchored proteins
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.45506
eLife 8 2019-09-04

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