1. Figure 3 Rainbow of p53 mutants
Figure 3 | Rainbow of p53 mutants. a | The graph shows the general trends, based on published data, in the ability of the various classes of p53 mutants to transactivate canonical p53 target genes (red bars), or to induce p53-dependent cellular responses, such as apoptosis (blue bars), when expressed in p53-null cells. Mutations in the amino-terminal (AT) region of p53, comprising the first transactivation domain, tend to result in at least a partial loss of transcriptional activity compared with WT p53, but apoptotic and cellular growth inhibition responses are generally preserved. p53 DNA-binding domain (DBD) mutations are completely nonfunctional; oligomerization domain (OD) mutants also tend to have complete loss of function (LOF), although some OD mutants retain partial activity. b | This graph shows the general trends in the ability of p53 DNA-binding domain (DBD) mutants to, upon exposure to genotoxic stresses, exhibit dominant-negative (DN) activity when in the heterozygous state, owing to hetero-oligomerization, and gain-of-function (GOF) activities when expressed in the absence of wild-type (WT) p53; the degree of p53 functionality is also indicated for the p53 wild-type (TP53+/+), heterozygous (TP53+/−), and null (TP53−/−) states, for comparison. p53 DBD mutants co-occurring with a WT p53 typically reduce the capacity for both canonical p53 target-gene expression and cellular responses, owing to DN activity (DBD-DN). In the absence of WT p53, DBD-mutants with GOF activity (DBD-GOF) generally further dampen canonical p53-driven cellular responses and/or acquire novel, noncanonical pro-tumorigenic functions. Data on p53 AT or OD mutants co-occurring with WT p53 are not available, but one could envisage that functional consequence will be similar to those of the TP53+/− state, without any DN effect. Moreover, GOF effects of AT and OD mutations have not been demonstrated. c | This cartoon depicts the various classes of mutant p53 — that is, the 'rainbow of p53 mutants' — based on their capacity to differentially transactivate target genes when expressed on a p53-null background, except in the case of DBD-DN mutants, which relates to the heterozygous state. WT and mutant p53 monomers are represented in yellow and red, respectively. PF, partial function; p53RE, p53 response element; TFRE, transcription-factor response element.
Sabapathy, K. & Lane, D. P. (2017) Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Nat. Rev. Clin. Oncol. doi: /nrclinonc