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STOPAPCG1IMP

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

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

STOPAPCG1IMP project word cloud

Explore the words cloud of the STOPAPCG1IMP project. It provides you a very rough idea of what is the project "STOPAPCG1IMP" about.

screen regulation fzr flyorf understand spatiotemporal gain vivo sustain individual transcriptional drosophila arrest clues interactors screens function requirement cell tissues autonomous performed output temporally regulator mechanisms fizzy induce cycle anaphase g1 biology functional library terminal link later differentiation additionally neurodegeneration subsequent activation signalling turn gained developmental diseases establishing coactivator apc initial spatial assayed pattern retina proteomic genes insights components cyclosome overexpresion encode complementary developmentally cancer cascades overproliferating eye expression discovered modulates aberrant rap critical proliferation initially patterning newly posttranslational gene coupling

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 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.	UK (CAMBRIDGE)	coordinator	195˙454.00

Map

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

List of publications.
year	authors and title	journal	last update
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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