Innovating Works

PID2021-127710OB-I00

Financiado
DEFINIR LOS PROCESOS CELLULARES A TRAVES DE LOS CUALES EL P53 SUPRIME LOS TUMORE...
MECHANISMS CRITICAL FOR TUMOR SUPPRESSION DOWNSTREAM OF P53 REMAIN LARGELY UNEXPLORED, DESPITE THEIR GREAT INTEREST FOR CANCER BIOLOGY. RECENT STUDIES, INCLUDING OURS, HAVE CHALLENGED THE SIGNIFICANCE OF CLASSICAL P53 DOWNSTREAM F... MECHANISMS CRITICAL FOR TUMOR SUPPRESSION DOWNSTREAM OF P53 REMAIN LARGELY UNEXPLORED, DESPITE THEIR GREAT INTEREST FOR CANCER BIOLOGY. RECENT STUDIES, INCLUDING OURS, HAVE CHALLENGED THE SIGNIFICANCE OF CLASSICAL P53 DOWNSTREAM FUNCTIONS (OF APOPTOTIC CELL DEATH, CELL CYCLE ARREST, AND CELL SENESCENCE) IN TUMOR SUPPRESSION. OUR HYPOTHESIS IS THAT THE P53-MEDIATED TUMOUR SUPPRESSION RELIES ON COLLECTIVE AND COOPERATIVE ACTIVATION OF THE P53 TARGET GENE NETWORK. GENETIC SCREENS AND GENETICAL MODIFIED MOUSE MODELS HAVE PROVIDED USEFUL TOOLS FOR REVEALING THE IMPORTANCE OF NUMEROUS P53-MEDIATED TARGET GENES AND BIOLOGICAL FUNCTIONS TO TUMOUR SUPPRESSION THAT COMPRISE A COOPERATIVE TUMOUR SUPPRESSION NETWORK DOWNSTREAM OF P53. THE RELATIVE IMPORTANCE OF DIFFERENT TARGET GENES DOWNSTREAM OF P53 COULD VARY BASED ON CONTEXT, SUCH AS THE CELL TYPE, MUTATIONAL LANDSCAPE OR STRESS PLACED ON THE CELL. DIFFERENT COMPONENTS OF THE P53 PATHWAY MIGHT ALSO HAVE DISTINCT ROLES IN TUMOUR SUPPRESSION DEPENDING ON WHETHER P53 IS ACTING TO SUPPRESS SPONTANEOUS CANCER INITIATION OR CANCER PROGRESSION IN THE CONTEXT OF ONCOGENIC DRIVERS. THE RNA BINDING PROTEIN ZMAT3 AND E3-UBIQUITIN LIGASE RNF144B, WERE THE MOST POTENT HITS FROM OUR SCREENS. USING SEVERAL INDEPENDENT ASSAYS WE HAVE VALIDATED ZMAT3 AND RNF144B AS BONA FIDE TUMOUR SUPPRESSORS. UNDERSTANDING THE MECHANISMS, BY WHICH ZMAT3 AND RNF144B ACT IN HEALTHY AND CANCER CELLS, AND HOW THEY MEDIATE THEIR TUMOUR SUPPRESSIVE FUNCTION IS THE MAJOR FOCUS OF THIS PROPOSAL. THE SUCCESS OF THIS PROJECT IN IDENTIFYING UNKNOWN MOLECULAR REGULATORY NODES OF P53 TRANSCRIPTIONAL NETWORK AND WILL INCREASE OUR UNDERSTANDING OF THE MOLECULAR INTERACTIONS REGULATING P53 LOSS–MEDIATED CANCER DEVELOPMENT AND PROGRESSION, WHICH WILL GENERATE SCIENTIFIC KNOWLEDGE THAT WILL PROVIDE A FOUNDATION FOR IMPROVING CANCER THERAPY. ANCER\MUERTE CELLULAR\REPARACION DE ADN\SUPRESION TUMORAL\P53 ver más
01/01/2021
UPF
230K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2021-01-01
Presupuesto El presupuesto total del proyecto asciende a 230K€
Líder del proyecto
UNIVERSITAT POMPEU FABRA No se ha especificado una descripción o un objeto social para esta compañía.
Total investigadores 321