Roles of P53 Family Structure and Function in Non-Canonical Response Element Binding and Activation

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jul 31

PMID 31357595

Citations 13

Authors

Bi-He Cai

Chung-Faye Chao

Hsiang-Chi Huang

Hsueh-Yi Lee

Reiji Kannagi

Jang-Yi Chen

Affiliations

Soon will be listed here.

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.

Citing Articles

A Simple and Affordable Method to Create Nonsense Mutation Clones of p53 for Studying the Premature Termination Codon Readthrough Activity of PTC124.

Chen C, Liao R, Yeh F, Lin Y, Wu T, Pastor A Biomedicines. 2023; 11(5).

PMID: 37238980 PMC: 10216193. DOI: 10.3390/biomedicines11051310.

The Competition of Yin and Yang: Exploring the Role of Wild-Type and Mutant p53 in Tumor Progression.

Cai B, Sung Y, Chen C, Shaw J, Hsin I Biomedicines. 2023; 11(4).

PMID: 37189810 PMC: 10136317. DOI: 10.3390/biomedicines11041192.

Phylogenetic analysis of the MCL1 BH3 binding groove and rBH3 sequence motifs in the p53 and INK4 protein families.

McGriff A, Placzek W PLoS One. 2023; 18(1):e0277726.

PMID: 36696417 PMC: 9876281. DOI: 10.1371/journal.pone.0277726.

PTC124 Rescues Nonsense Mutation of Two Tumor Suppressor Genes and to Repress HNSCC Cell Proliferation.

Wu M, Lu R, Yu S, Tsai Y, Lin Y, Bai Z Biomedicines. 2022; 10(11).

PMID: 36428516 PMC: 9687978. DOI: 10.3390/biomedicines10112948.

Protein of a thousand faces: The tumor-suppressive and oncogenic responses of p53.

Marques M, de Andrade G, Silva J, de Oliveira G Front Mol Biosci. 2022; 9:944955.

PMID: 36090037 PMC: 9452956. DOI: 10.3389/fmolb.2022.944955.

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