Fig. 2From: Soft Tissue Sarcomas and p53 MutationsModel investigating how mutational status affects p53 DNA-binding function. This model suggests that p53 mutation type can affect p53 protein assembling and therefore functional characteristics of DNA binding. Frameshift mutations (fs) result in a shortened or missing protein that is unable to oligomerize with the wild-type protein. As long as a wild-type protein is still present, it could function on a reduced dosage (left section). Presence of a non-frameshift mutation (non-fs) causes a mutant protein that can oligomerize. In addition to a functional loss because of the mutation other possibilities are described that are dependent on the mutational sites and events. The mutant protein can oligomerize with wild-type protein, thereby exerting a dominant negative effect at binding to the normal DNA binding sites or gain a new function at binding to other (altered) DNA binding sites. Alternatively, it can bind to another mutant p53, giving rise to a gain-of-function protein (right section). Furthermore, changed protein conformation could alter transactivation properties of other proteins.Back to article page