CTS1 - A P53-DERIVED CHIMERIC TUMOR-SUPPRESSOR GENE WITH ENHANCED IN-VITRO APOPTOTIC PROPERTIES

The clinical potential of the p53 tumor suppressor gene is being evalu ated currently for gene therapy of cancer. We have built a variant of wild-type p53, chimeric tumor suppressor 1 (CTS1), in which we have re placed the domains that mediate its inactivation. CTS1 presents some v ery interesting properties: (a) enhanced transcriptional activity; (b) resistance to the inactivation by oncogenic forms of p53; (c) resista nce to the inactivation by MDM2; (d) lower sensitivity to E6-induced d egradation; (e) ability to suppress cell growth; and (f) faster induct ion of apoptosis. Thus, CTS1 is an improved tumor suppressor and an al ternative for the treatment of wild-type p53-resistant human tumors by gene therapy.