Abstract
The p53 canonical consensus sequence is a 10-bp repeat of PuPuPuC(A/T)(A/T)GPyPyPy, separated by a spacer with up to 13 bases. C(A/T)(A/T)G is the core sequence and purine (Pu) and pyrimidine (Py) bases comprise the flanking sequence. However, in the p53 noncanonical sequences, there are many variations, such as length of consensus sequence, variance of core sequence or flanking sequence, and variance in number of bases making up the spacer or AT gap composition. In comparison to p53, the p53 family members p63 and p73 have been found to have more tolerance to bind and activate several of these noncanonical sequences. The p53 protein forms monomers, dimers, and tetramers, and its nonspecific binding domain is well-defined; however, those for p63 or p73 are still not fully understood. Study of p63 and p73 structure to determine the monomers, dimers or tetramers to bind and regulate noncanonical sequence is a new challenge which is crucial to obtaining a complete picture of structure and function in order to understand how p63 and p73 regulate genes differently from p53. In this review, we will summarize the rules of p53 family non-canonical sequences, especially focusing on the structure of p53 family members in the regulation of specific target genes. In addition, we will compare different software programs for prediction of p53 family responsive elements containing parameters with canonical or non-canonical sequences.
Highlights
The p53 canonical consensus sequence is a 10-bp repeat of PuPuPuC(A/T)(A/T)GPyPyPy, separated by a spacer with up to 13 bases
The Flt1-T single-nucleotide polymorphism (SNP) promoter can be activated by p53 because the up-strand contains an estrogen responsive element (ERE), and p53 almost no longer activates the Flt1-T SNP promoter with mutation of ERE [13]
Site 1 could be bound by all p53 family members, but site 2 could only be bound by p53 but not p63 or p73 [20]
Summary
The p53 canonical consensus sequence is a 10-bp repeat of PuPuPuC(A/T)(A/T)GPyPyPy (Figure 1A) [6]. Incubation of the p53 protein with labeled p53 whole-site and different lengths of consensus sequence unlabeled competitors were analyzed by EMSA. 1.5× half-site competitor could compete with the whole-site binding [8]. The consecutive 1.5× half-site is activated by p53 more strongly than the nonconsecutive 1.5× half-site [8]. P63 was able to activate a p53 half-site on KRT14 promoter, and p53 could activate the mutants with extended sequence as whole-site of KRT14 promoter [16]. Because p53 could repress the KRT14 promoter through the SP1 binding site [17], the mutants with extended sequence, such as 1.5× half-site on KRT14 promoter, were still not activated by p53 [16]
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