title: Mechanisms of mutant p53 stabilization in cancer.
abstract: p53 transactivates cell cycle inhibitory, apoptosis or senescence-related genes in response to DNA damage to protect the genetic integrity of the cell. Highlighting its critical tumor suppressor functions, p53 is mutated, lost, or functionally inactivated in nearly all cancers. When mutated within its core DNA binding domain, p53's normal instability is abrogated, and oncogenic gain-of-function properties are observed accompanied by massive accumulation of steady state mutant p53 protein levels relative to the low or undetectable steady state level of wild-type (WT) p53 in normal cells. Mutation of p53 may affect its stability through a combination of mutant p53's inherent biochemical and biophysical properties as well as pathways aberrantly activated in genetically damaged cells. The increased stability of mutant p53 proteins is key to its ability to accumulate to high levels and phenotypically exhibit "gain-of-function" properties. In this chapter we will address the multifaceted ways in which intrinsic mutant p53 properties intersect with emergent properties of cancer cells to yield the stable mutant p53 phenotype.
authors.affiliation: Division of Hematology, Oncology, and Palliative Care, VCU Massey Cancer Center, Virginia Commonwealth University, 1201 E. Marshall St., Box 980070, Richmond, VA, 23298, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Frum
authors.forename: Steven R
authors.initials: SR
authors.lastname: Grossman
mesh_terms: D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2