ACTINONSRF

MAL: an actin-regulated SRF transcriptional coactivator

 Coordinatore THE FRANCIS CRICK INSTITUTE LIMITED 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 1˙889˙995 €
 EC contributo 1˙889˙995 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2010-AdG_20100317
 Funding Scheme ERC-AG
 Anno di inizio 2011
 Periodo (anno-mese-giorno) 2011-10-01   -   2016-09-30

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    CANCER RESEARCH UK

 Organization address address: ST JOHN STREET 407 ANGEL BUILDING
city: LONDON
postcode: EC1V 4AD

contact info
Titolo: Ms.
Nome: Holly
Cognome: Elphinstone
Email: send email
Telefono: 442073000000
Fax: 442073000000

UK (LONDON) beneficiary 0.00
2    THE FRANCIS CRICK INSTITUTE LIMITED

 Organization address address: 215 Euston Road, Gibbs Building
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Dr.
Nome: Richard
Cognome: Treisman
Email: send email
Telefono: 442073000000
Fax: 442073000000

UK (LONDON) hostInstitution 1˙889˙995.00
3    THE FRANCIS CRICK INSTITUTE LIMITED

 Organization address address: 215 Euston Road, Gibbs Building
city: LONDON
postcode: NW1 2BE

contact info
Titolo: Ms.
Nome: Heather Joanne
Cognome: Woods
Email: send email
Telefono: 442076000000

UK (LONDON) hostInstitution 1˙889˙995.00

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 Word cloud

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activation    molecular    coactivator    shuttling    nuclear    proteins    binding    dynamics    interaction    biology    regulated    iquest    nucleocytoplasmic    transcriptional    mal    domain    transcription    srf    actin    rpel   

 Obiettivo del progetto (Objective)

'MAL: an actin-regulated SRF transcriptional coactivator

Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology: ¿ Actin as a transcriptional regulator ¿ Actin as a signalling molecule ¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function

We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.'

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