A/T gap tolerance in the core sequence and flanking sequence requirements of non-canonical p53 response elements

Cai, Bi-He; Chao, Chung-Faye; Lin, Hwang-Chi; Huang, Huaying; Kannagi, Reiji; Chen, Jang-Yi

doi:10.1093/jb/mvw005

Cited by 3 publications

(5 citation statements)

References 50 publications

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“…Therefore, CATTAG is a functional core sequence that contains four AT gaps. In addition, a six-base AT gap CATATATG core sequence was the maximum AT gap in the p53-responsive element that could be upregulated by p53 and p63 (Figure 1B) [24]. AT gaps of 3, 5, 7, or 8 bases were not bound and activated by p53 (Figure 1C) [23,24].…”

Section: Noncanonical Sequences Of the P53 Family Regulation Sitesmentioning

confidence: 99%

“…This means that only five bases between two core sequences could be activated by p63. In reporter assays, both p53 and TAp63γ could activate six bases between two core sequences, but only TAp63γ could activate five bases between two core sequences [24]. Therefore, p63 could bind and activate a consensus sequence with a -1 spacer.…”

Section: Other Sequence Variation Also Influences P53 Family Activitymentioning

confidence: 99%

“…p53 with deletion of the nonspecific domain binds to 4 AT gap and 6 AT gap, but the binding is much weaker than towards the 2AT gap [23,24]. It is necessary to avoid nonspecific binding in each p53 family member in experiments.…”

Section: Structure Of P53 Family Members and Its Relationship To Tmentioning

confidence: 99%

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Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation

Cai

Chao

Huang

et al. 2019

IJMS

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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.

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Section: Noncanonical Sequences Of the P53 Family Regulation Sitesmentioning

confidence: 99%

Section: Other Sequence Variation Also Influences P53 Family Activitymentioning

confidence: 99%

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Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation

Cai

Chao

Huang

et al. 2019

IJMS

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“…Lovastatin was able to induce TP63 transactivation through phosphorylation of the AMPK-p38MAPK-TAp63 cascade to cause hypopharyngeal carcinoma FaDu cell death [ 97 ]. TAp63 can active PUMA (p53 upregulated modulator of apoptosis) [ 98 , 99 ], and interferon-α can induce TP63 and PUMA expression in hepatocyte derived cellular carcinoma cell line HuH7 cells [ 100 ].…”

Section: P63 Activation Drugsmentioning

confidence: 99%

P63 and P73 Activation in Cancers with p53 Mutation

et al. 2022

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The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed.

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“…AMPK is a positive regulator of autophagy [ 25 ] and can also phosphorylate p53 family members to enhance their anticancer function [ 26 , 27 ]. p53, p63, and p73 can activate PUMA, which induces cell apoptosis [ 28 , 29 , 30 ]. However, the PI3K-AKT pathway can suppress PUMA expression [ 31 , 32 ], and as shown in Figure 2 , mutant p53 can prevent cell apoptosis through the PI3K-AKT-PUMA pathway.…”

mentioning

confidence: 99%

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

et al. 2023

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A/T gap tolerance in the core sequence and flanking sequence requirements of non-canonical p53 response elements

Cited by 3 publications

References 50 publications

Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation

Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation

P63 and P73 Activation in Cancers with p53 Mutation

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

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