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Contenuto archiviato il 2022-12-23

Environmental carcinogens and mutation spectra in P53 tumour suppresor gene and other critical genes

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

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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

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Costo totale
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