title: Structural studies on mechanisms to activate mutant p53.
abstract: The design of a broad-spectrum cancer drug would provide enormous clinical benefits to treat cancer patients. Most of cancerous cells have a mutation in the p53 gene that results in an inactive mutant p53 protein. For this reason, p53 is a prime target for the development of a broad-spectrum cancer drug. To provide the atomic information to rationally design a drug to recover p53 activity is the main goal of the structural studies on mutant p53. We review three mechanisms that influence p53 activity and provide information about how reactivation of mutant p53 can be achieved: stabilization of the active conformation of the DNA-binding domain of the protein, suppression of missense mutations in the DNA-binding domain by a second-site mutation, and increased transactivation.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, D.F., Mexico, viadiu@unam.mx.
authors.forename: Hector
authors.initials: H
authors.lastname: Viadiu
authors.forename: Gilberto
authors.initials: G
authors.lastname: Fronza
authors.forename: Alberto
authors.initials: A
authors.lastname: Inga
mesh_terms: D003461:Crystallography; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53