Obiettivo THIS ADDITIONAL PROPOSAL HAS BEEN FORMULATED FOR FUNCTIONAL CHARACTERISATION OF P53 ONcopRoTEINs EXPRESSED IN NATURALLY OCCURRING TUMOURS. P53 ONCOGENE IS MUTATED WITH REMARKABLy HIGH FREQUENCE IN MOST DIFFERENT TYPES OF HUMAN CANCER. ALTHOUGH SUCH MUTATIONS HAVE BEEN PUBLISHED IN NUMEROUS PAPERS, NO CLEAR CORRELATION BETWEEN CERTAIN TYPES OF CANCER AND CERTAIN MUTATIONAL SPECTRA CAN BE DRAWN SO FAR. WE PROPOSE THAT p53 IS A MULTIFUNCTIONAL PROTEIN AND ITS FUNCTIONAL STATE DEPENDS ON DIFFERENT FACTORS, INCLUDING INTERACTIONS WITH OTHER CELLULAR AND/OR VIRAL PROTEINS, DIFFERENT POSTTRANSLATIONAL MODIFICATIONS, CONFORMATIONAL STATE ETC. SUCH DIFFERENT FUNCTIONAL STATES OF THE P53 PROTEIN SHOULD BE REFLECTED ON THE LEVEL OF ITS BIOCHEMICAL AND BIOLOGICAL ACTIVITIES: ABILITY TO INTERACT WITH OTHER PROTEINS AND DNA*, ABILITY TO IMMORTALIZE CELLS, TO TRANSFORM THEM AND SUPPORT THEIR ENTRY INTO APOPTOSIS. WE PROPOSE TO ISOLATE P53 cDNA-S FROM CERTAIN DEFINED TYPES OF HUMAN TUMOURS AND ANALYSE THEIR BIOLOGICAL AND BIOCHEMICAL PROPERTIES- FOR THAT PURPOSE WE COLLECT SAMPLES FROM DIFFERENT TUMORS, ISOLATE cDNA BY POLYMERASE CHAIN REACTION TECHNIQUE AND EXPRESS THE CORRESPONDING PROTEINS IN VIVO IN CULTIVATED CELLS USING EUKARYOTIC EXPRESSION VECTORS. PROTEINS OBTAINED BY THIS PROCEDURE WILL BE ASSAYED BY THEIR FUNCTIONAL PROPERTIES. ALSO, AT THE SAME TIME WE WOULD ISOLATE OTHER ONCOPROTEINS FROM HUMAN TUMOURS (MYC, MAX, ETC.) AND ANALYSE THEIR ROLE IN MODULATING THE ACTIVITY OF BOTH WILD-TYPE AND CORRESPONDING MUTANT FORMS OF P53. WE HOPE THAT THE RESULTS OF THIS PROJECT WILL ALLOW US TO GROUP DIFFERENT MUTANT FORMS OF P53 OCCURRING IN HUMAN TUMOURS ACCORDING TO THEIR FUNCTIONAL STATES RATHER THAN ACCORDING TO MORE FORMAL CRITERIA SUCH AS THE LOCALISATION OF MUTATIONS ALONG THE AMINO ACID CHAIN, TYPE OF NUCLEOTIDE TRANSITION ETC. THIS KNOWLEDGE COULD MAKE IT POSSIBLE TO CONSTRUCT METHODS OF EARLY DIAGNOSIS OF HUMAN CANCER BASED ON DEFINITION OF THE STATUS OF P53 IN CELLS, WHICH HAS NOT BEEN POSSIBLE SO FAR. *ABILITY TO MODULATE DNA TRANSCRIPTION, REPLICATION AND REPAIR Programma(i) IC-PECO/COPERNICUS - Scientific and technological cooperation between the European Community and European non-member countries, 1992- Argomento(i) 01 - CEEC participation in ENVIRONMENT programme Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore Centre International de Recherche sur le Cancer Contributo UE Nessun dato Indirizzo 150 cours Albert Thomas 69372 Lyon Francia Mostra sulla mappa Costo totale Nessun dato Partecipanti (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto University of Tartu Estonia Contributo UE Nessun dato Indirizzo 2,Jakobi 2400 Tartu Mostra sulla mappa Costo totale Nessun dato