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STOPAPCG1IMP

Spatial-temporal regulation of APC/C, its role on G1 arrest and impact on terminal differentiation

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Project "STOPAPCG1IMP" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.ac.uk

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 United Kingdom [UK]
 Project website http://www.gen.cam.ac.uk/research-groups/kimata
 Total cost 195˙454 €
 EC max contribution 195˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2017-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 195˙454.00

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 Project objective

Coupling the cell-autonomous process of the cell cycle with spatiotemporal clues that promote the differentiation process is a major challenge in developmental biology. The retina aberrant in pattern (rap) gene was initially identified as a retina differentiation and patterning gene in Drosophila. It was later discovered to encode Fizzy-related (Fzr), a coactivator of the cell cycle regulator, Anaphase Promoting Complex/Cyclosome (APC/C). This was a critical initial step towards establishing a link between differentiation and cell cycle regulation. This project aims to understand the coordination between mechanisms of proliferation and differentiation, with a particular focus on the APC/C complex. The requirement of individual APC/C components to sustain the developmentally controlled G1 arrest and its subsequent effects on terminal differentiation will be addressed. The transcriptional and posttranslational regulation of each APC/C component will be assayed during eye development. Next, functional APC/C interactors will be identified through two complementary screens. An in vivo gain-of-function overexpresion screen will be performed, to identify the genes that can induce cell cycle arrest in overproliferating tissues, using the newly developed FlyORF library. Additionally, a proteomic analysis of APC/C components will be performed to identify eye-specific APC/C interactors. With the information gained I will investigate how the activity and expression of the APC/C is spatial-temporally controlled by signalling cascades during eye development, and how the APC/C in turn modulates the activation and output of those signalling pathways. Overall, the insights from this project will contribute to our understanding of complex diseases such as cancer and neurodegeneration.

 Publications

year authors and title journal last update
List of publications.
2016 Francesco Meghini, Torcato Martins, Xavier Tait, Kazuyuki Fujimitsu, Hiroyuki Yamano, David M. Glover, Yuu Kimata
Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit
published pages: 12607, ISSN: 2041-1723, DOI: 10.1038/ncomms12607
Nature Communications 7 2019-06-13
2017 Torcato Martins, Francesco Meghini, Francesca Florio, Yuu Kimata
The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling
published pages: 67-80, ISSN: 1534-5807, DOI: 10.1016/j.devcel.2016.12.005
Developmental Cell 40/1 2019-06-13

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