GADD45&P38SIGNALING

Role of the Gadd45 family and p38 MAPK in tumor suppression and autoimmunity

 Coordinatore  

Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.

 Nazionalità Coordinatore Non specificata
 Totale costo 1˙755˙805 €
 EC contributo 17˙558 €
 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)
 Anno di inizio 2008
 Periodo (anno-mese-giorno) 2008-09-01   -   2014-08-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

 Organization address address: CALLE SERRANO 117
city: MADRID
postcode: 28006

contact info
Titolo: Dr.
Nome: Jesús
Cognome: Salvador
Email: send email
Telefono: -5854594
Fax: -3720550

ES (MADRID) hostInstitution 0.00
2    AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

 Organization address address: CALLE SERRANO 117
city: MADRID
postcode: 28006

contact info
Titolo: Ms.
Nome: Ana Maria
Cognome: De La Fuente
Email: send email
Telefono: 34915681709
Fax: 34915681709

ES (MADRID) hostInstitution 0.00

Mappa


 Word cloud

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apoptosis    therapeutic    tumor    cell    lupus    mice       cancer    epigenetic    autoimmune    molecular    gadd    phosphorylation    family    tyr    suppression    proliferation    disease    activation    diseases    vivo    human    autoimmunity    mechanisms   

 Obiettivo del progetto (Objective)

'Gadd45 family proteins play a critical role in genomic stability, cell cycle regulation proliferation and apoptosis. Gadd45a is activated by the tumor suppressor gene p53, which is mutated in >50% of human tumors. The lack of GADD45a in mice leads to spontaneous development of an autoimmune disease similar to systemic lupus erythematosus. The molecular mechanisms that cause autoimmunity are poorly understood. Recent evidence suggests that p38 activation is involved in autoimmune development and tumor suppression. We found that Gadd45a negatively regulates p38 activity in T cells by preventing phosphorylation on Tyr323. Inhibition of Tyr323p38 phosphorylation is a potential therapeutic target in several types of leukemia and autoimmune diseases, including lupus and rheumatoid arthritis. The main goals of this project are a) to study the in vivo function of the Gadd45 family and p38 in tumor suppression and autoimmunity, and b) to analyze their molecular mechanisms to identify targets for disease treatment. We will dissect the signaling pathways involved in development of autoimmunity and cancer using a multidisciplinary approach that combines mouse genetic, human epigenetic, biochemical, molecular biological and immunological techniques. Our project involves the characterization of murine models deficient in each member of the Gadd45 family (Gadd45a, Gadd45b, Gadd45g), as well as double- and triple-knockout mice, development of a knock-in model for p38a, in vivo and in vitro analysis of T cell activation, proliferation, apoptosis and differentiation, epigenetic studies of potential targets, and finally, validation of these results in autoimmune disease and cancer patients. The results of this project will help identify new therapeutic targets for autoimmune diseases and/or cancer.'

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