Abstract
The p53 gene encodes a transcription factor that is composed of several functional domains: the N-terminal transactivation domain, the central sequence-specific DNA binding domain, the tetramerization domain, and the highly basic C-terminal regulatory domain (CTD). The p53 CTD is a nonspecific DNA binding domain that is subject to extensive post-translational modifications. However, the functional significance of the p53 CTD remains unclear. The role of this domain in the regulation of p53 functions is explored by comparing the activity of ectopically expressed wild-type (WT) p53 protein to that of a truncated mutant lacking the 24 terminal amino acids (Δ24). Using quantitative real time PCR and chromatin Immuno-Precipitation experiments, a p53 CTD deletion is shown to alter the p53-dependent induction of a subset of its target genes due to impaired specific DNA binding. Moreover, p53-induced growth arrest and apoptosis both require an intact p53 CTD. These data indicate that the p53 CTD is a positive regulator of p53 tumor suppressor functions.
Highlights
The role of the conserved basic C terminus of p53 remains elusive
After transfection in H1299 cells, p53 WT and p53⌬24 are both localized in the nucleus. These results argue that the p53 C-terminal regulatory domain (CTD) may, influence p53 target gene selectivity
It is shown that the CTD is needed for all p53 activities that were tested and that this effect is likely due to impaired DNA binding to a subset of its target genes
Summary
The role of the conserved basic C terminus of p53 remains elusive. Results: The C terminus of p53 controls target gene selectivity and is needed for cellular responses. The functional significance of the p53 CTD remains unclear The role of this domain in the regulation of p53 functions is explored by comparing the activity of ectopically expressed wild-type (WT) p53 protein to that of a truncated mutant lacking the 24 terminal amino acids (⌬24). P53-induced growth arrest and apoptosis both require an intact p53 CTD These data indicate that the p53 CTD is a positive regulator of p53 tumor suppressor functions. P53⌬24 is unable to induce critical p53 functions, such as apoptosis or cell cycle arrest These data support an obligatory and positive role for the p53 CTD in p53 tumor suppressor functions
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