scholarly journals p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2885
Author(s):  
Anđela Horvat ◽  
Ana Tadijan ◽  
Ignacija Vlašić ◽  
Neda Slade
Keyword(s):  
Dna Sequences ◽  
Target Genes ◽  
Biological Activities ◽  
Expression Patterns ◽  
Family Members ◽  
Growth Control ◽  
P53 Family ◽  
Colorectal Tumorigenesis ◽  
Normal Functions ◽  
P53 Tumor Suppressor Protein

The p53 tumor suppressor protein is crucial for cell growth control and the maintenance of genomic stability. Later discovered, p63 and p73 share structural and functional similarity with p53. To understand the p53 pathways more profoundly, all family members should be considered. Each family member possesses two promoters and alternative translation initiation sites, and they undergo alternative splicing, generating multiple isoforms. The resulting isoforms have important roles in carcinogenesis, while their expression is dysregulated in several human tumors including colorectal carcinoma, which makes them potential targets in cancer treatment. Their activities arise, at least in part, from the ability to form tetramers that bind to specific DNA sequences and activate the transcription of target genes. In this review, we summarize the current understanding of the biological activities and regulation of the p53/p73 isoforms, highlighting their role in colorectal tumorigenesis. The analysis of the expression patterns of the p53/p73 isoforms in human cancers provides an important step in the improvement of cancer therapy. Furthermore, the interactions among the p53 family members which could modulate normal functions of the canonical p53 in tumor tissue are described. Lastly, we emphasize the importance of clinical studies to assess the significance of combining the deregulation of different members of the p53 family to define the outcome of the disease.

scholarly journals Evaluating the Influence of a G-Quadruplex Prone Sequence on the Transactivation Potential by Wild-Type and/or Mutant P53 Family Proteins through a Yeast-Based Functional Assay

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 277
Author(s):  
Paola Monti ◽  
Vaclav Brazda ◽  
Natália Bohálová ◽  
Otília Porubiaková ◽  
Paola Menichini ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Relative Activity ◽  
Gene Organization ◽  
Functional Assay ◽  
Wild Type ◽  
P53 Family ◽  
Transactivation Potential ◽  
G Quadruplex

P53, P63, and P73 proteins belong to the P53 family of transcription factors, sharing a common gene organization that, from the P1 and P2 promoters, produces two groups of mRNAs encoding proteins with different N-terminal regions; moreover, alternative splicing events at C-terminus further contribute to the generation of multiple isoforms. P53 family proteins can influence a plethora of cellular pathways mainly through the direct binding to specific DNA sequences known as response elements (REs), and the transactivation of the corresponding target genes. However, the transcriptional activation by P53 family members can be regulated at multiple levels, including the DNA topology at responsive promoters. Here, by using a yeast-based functional assay, we evaluated the influence that a G-quadruplex (G4) prone sequence adjacent to the p53 RE derived from the apoptotic PUMA target gene can exert on the transactivation potential of full-length and N-terminal truncated P53 family α isoforms (wild-type and mutant). Our results show that the presence of a G4 prone sequence upstream or downstream of the P53 RE leads to significant changes in the relative activity of P53 family proteins, emphasizing the potential role of structural DNA features as modifiers of P53 family functions at target promoter sites.

scholarly journals ASPP1 and ASPP2: Common Activators of p53 Family Members

2004 ◽  
Vol 24 (3) ◽  
pp. 1341-1350 ◽  
Author(s):  
Daniele Bergamaschi ◽  
Yardena Samuels ◽  
Boquan Jin ◽  
Sai Duraisingham ◽  
Tim Crook ◽  
...  
Keyword(s):  
Rna Interference ◽  
Tumor Growth ◽  
Target Genes ◽  
Family Members ◽  
Mutant P53 ◽  
P53 Family ◽  
P53 Target Genes

ABSTRACT We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21WAF-1/CIP1. The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21WAF-1/CIP1. Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.

scholarly journals MiR-92 Family Members Form a Cluster Required for Notochord Tubulogenesis in Urochordate Ciona savignyi

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 406
Author(s):  
Libo Yang ◽  
Xiaoming Zhang ◽  
Chengzhang Liu ◽  
Jin Zhang ◽  
Bo Dong
Keyword(s):  
Signaling Pathways ◽  
Planar Cell Polarity ◽  
Target Genes ◽  
Expression Patterns ◽  
Family Members ◽  
Mitogen Activated Protein Kinase ◽  
Mirna Cluster ◽  
Ciona Savignyi ◽  
Larval Stages ◽  
Regulatory Processes

MicroRNAs are frequently clustered in the genome and polycistronically transcribed, regulating targeted genes in diverse signaling pathways. The miR-17-92 cluster is a typical miRNA cluster, playing crucial roles in the organogenesis and homeostasis of physiological processes in vertebrates. Here, we identified three miRNAs (csa-miR-92a, csa-miR-92b, and csa-miR-92c) that belonged to the miR-92 family and formed a miRNA cluster in the genome of a urochordate marine ascidian Ciona savignyi. Except for miR-92a and miR-92b, other homologs of the vertebrate miR-17-92 cluster members could not be identified in the Ciona genome. We further found that the mature sequences of urochordate miR-92 family members were highly conserved compared with the vertebrate species. The expression pattern revealed that three miR-92 family members had consistent expression levels in adult tissues and were predominantly expressed in heart and muscle tissue. We further showed that, at the embryonic and larval stages, csa-miR-92c was expressed in the notochord of embryos during 18–31 h post fertilization (hpf) by in situ hybridization. Knockout of csa-miR-92c resulted in the disorganization of notochord cells and the block of lumen coalescence in the notochord. Fibroblast growth factor (FGF), mitogen-activated protein kinase (MAPK), and wingless/integrated (Wnt)/planar cell polarity (PCP) signaling pathways might be involved in the regulatory processes, since a large number of core genes of these pathways were the predicted target genes of the miR-92 family. Taken together, we identified a miR-92 cluster in urochordate Ciona and revealed the expression patterns and the regulatory roles of its members in organogenesis. Our results provide expression and phylogenetic data on the understanding of the miR-92 miRNA cluster’s function during evolution.

scholarly journals Identification and expression analysis of bovine ANGPTL gene family

2010 ◽  
Vol 56 (4) ◽  
pp. 445-453 ◽  
Author(s):  
Zhengbing Guan ◽  
Guolin Cai ◽  
Junyong Sun ◽  
Jian Lu
Keyword(s):  
Gene Family ◽  
Expression Analysis ◽  
Biological Activities ◽  
Expression Patterns ◽  
Family Members ◽  
Coiled Coil ◽  
Amino Acid Sequences ◽  
Pcr Analysis ◽  
Important Species ◽  
Real Time Quantitative Pcr

Abstract Encoded by seven genes, angiopoietin-like (ANGPTL) family members structurally similar to the angiogenic regulating factor angiopoietin are known to possess biological activities in angiogenesis and metabolism. Here we reports for the first time the identification and expression analysis of all the seven members of bovine ANGPTL gene family, which were designated bANGPTL1 to bANGPTL7 in order. The seven bANGPTL genes consist of 4-9 exons, span 3800-43000 bp and are located on different chromosomes. The deduced amino acid sequences of the members all possess an N-terminal coiled-coil domain and a C-terminal fibrinogen-like domain, both characteristics of angiopoietins. Phylogenetic analysis showed that the 32 identified ANGPTL homologs from 9 species could be classified into two major groups. Real-time quantitative PCR (Q-PCR) analysis revealed that the bANGPTL family members have different expression patterns. This study will be helpful for investigation on the biological role of the bANGPTL family in this economically important species. Furthermore, it provides an insight into the molecular evolution of the emerging ANGPTL family.

scholarly journals Molecular and Biological Properties of Snakins: The Foremost Cysteine-Rich Plant Host Defense Peptides

2020 ◽  
Vol 6 (4) ◽  
pp. 220
Author(s):  
Tao Su ◽  
Mei Han ◽  
Dan Cao ◽  
Mingyue Xu
Keyword(s):  
Host Defense ◽  
Plant Pathogens ◽  
Biological Activities ◽  
Expression Patterns ◽  
Family Members ◽  
Biological Properties ◽  
Plant Host ◽  
Host Defense Peptides ◽  
Wide Range ◽  
Defense Peptides

Plant host defense peptides (HDPs), also known as antimicrobial peptides (AMPs), are regarded as one of the most prevalent barriers elaborated by plants to combat various infective agents. Among the multiple classes of HDPs, the Snakin class attracts special concern, as they carry 12 cysteine residues, being the foremost cysteine-rich peptides of the plant HDPs. Also, their cysteines are present at very highly conserved positions and arranged in an extremely similar way among different members. Like other plant HDPs, Snakins have been shown to exhibit strong antifungal and antibacterial activity against a wide range of plant pathogens. Moreover, they display diversified biological activities in many aspects of plant growth and the development process. This review is devoted to present the general characters of the Snakin class of plant HDPs, as well as the individual features of different Snakin family members. Specifically, the sequence properties, spatial structures, distributions, expression patterns and biological activities of Snakins are described. In addition, further detailed classification of the Snakin family members, along with their possible mode of action and potential applications in the field of agronomy and pathology are discussed.

scholarly journals The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
R. A. G. Khammissa ◽  
J. Fourie ◽  
M. H. Motswaledi ◽  
R. Ballyram ◽  
J. Lemmer ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Homeostasis ◽  
Dna Sequences ◽  
Target Genes ◽  
Biological Activities ◽  
Biological Effects ◽  
Active Form ◽  
Vitamin D Supplementation ◽  
Biologically Active ◽  
Bone Homeostasis

Vitamin D plays an important role in calcium homeostasis and bone metabolism, with the capacity to modulate innate and adaptive immune function, cardiovascular function, and proliferation and differentiation of both normal and malignant keratinocytes. 1,25(OH)2D, the biologically active form of vitamin D, exerts most of its functions through the almost universally distributed nuclear vitamin D receptor (VDR). Upon stimulation by 1,25(OH)2D, VDR forms a heterodimer with the retinoid X receptor (RXR). In turn, VDR/RXR binds to DNA sequences termed vitamin D response elements in target genes, regulating gene transcription. In order to exert its biological effects, VDR signalling interacts with other intracellular signalling pathways. In some cases 1,25(OH)2D exerts its biological effects without regulating either gene expression or protein synthesis. Although the regulatory role of vitamin D in many biological processes is well documented, there is not enough evidence to support the therapeutic use of vitamin D supplementation in the prevention or treatment of infectious, immunoinflammatory, or hyperproliferative disorders. In this review we highlight the effects of 1,25(OH)2D on bone and calcium homeostasis, on cancer, and refer to its effects on the cardiovascular and immune systems.

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

2019 ◽  
Vol 20 (15) ◽  
pp. 3681 ◽  
Author(s):  
Bi-He Cai ◽  
Chung-Faye Chao ◽  
Hsiang-Chi Huang ◽  
Hsueh-Yi Lee ◽  
Reiji Kannagi ◽  
...  
Keyword(s):  
Target Genes ◽  
P53 Protein ◽  
Consensus Sequence ◽  
Family Members ◽  
Structure And Function ◽  
Nonspecific Binding ◽  
Flanking Sequence ◽  
P53 Family ◽  
Core Sequence ◽  
And Function

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.

scholarly journals A feed-forward relay between Bicoid and Orthodenticle regulates the timing of embryonic patterning in Drosophila

2017 ◽  
Author(s):  
Rhea R. Datta ◽  
Jia Ling ◽  
Jesse Kurland ◽  
Xiaotong Ren ◽  
Zhe Xu ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Expression Patterns ◽  
Embryonic Patterning ◽  
Feed Forward ◽  
Dna Motif ◽  
Sequential Binding ◽  
Anterior Patterning

AbstractThe K50 homeodomain (K50HD) protein Orthodenticle (Otd) is critical for anterior patterning and brain and eye development in most metazoans. In Drosophila melanogaster, another K50HD protein, Bicoid (Bcd), has evolved to replace Otd’s ancestral function in embryo patterning. Bcd is distributed as a long-range maternal gradient and activates transcription of a large number of target genes including otd. Otd and Bcd bind similar DNA sequences in vitro, but how their transcriptional activities are integrated to pattern anterior regions of the embryo is unknown. Here we define three major classes of enhancers that are differentially sensitive to binding and transcriptional activation by Bcd and Otd. Class 1 enhancers are initially activated by Bcd, and activation is transferred to Otd via a feed-forward relay (FFR) that involves sequential binding of the two proteins to the same DNA motif. Class 2 enhancers are activated by Bcd, and maintained by an Otd-independent mechanism. Class 3 enhancers are never bound by Bcd, but Otd binds and activates them in a second wave of zygotic transcription. The specific activities of enhancers in each class are mediated by DNA motif variants preferentially bound by Bcd or Otd, and the presence or absence of sites for cofactors that interact with these proteins. Our results define specific patterning roles for Bcd and Otd, and provide mechanisms for coordinating the precise timing of gene expression patterns during embryonic development.

scholarly journals Distinct Evolutionary Profiles and Functions of microRNA156 and microRNA529 in Land Plants

2021 ◽  
Vol 22 (20) ◽  
pp. 11100
Author(s):  
Qi Xie ◽  
Xufeng Wang ◽  
Juan He ◽  
Ting Lan ◽  
Jiayu Zheng ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Target Genes ◽  
Sequence Similarity ◽  
Expression Patterns ◽  
Family Members ◽  
Land Plants ◽  
Small Rna Sequencing ◽  
Evolutionary Divergence ◽  
High Sequence Similarity ◽  
Functional Differences

MicroRNA156 (miR156) and miR529 have high sequence similarity and recognize overlapping sites in the same target genes, SQUAMOSA promoter binding protein-like (SPL or SBP box) genes, making it difficult to accurately distinguish their roles in regulatory networks that affect numerous biological functions. Here, we collected data about miR156 and miR529 family members from representative land plants and performed sequence comparisons, phylogenetic analysis, small RNA sequencing, and parallel analysis of RNA ends (PARE) analysis to dissect their evolutionary and functional differences. Although miR156 and miR529 are highly similar, there are differences in their mismatch-sensitive regions, which are essential for target recognition. In land plants, miR156 precursors are conserved mainly within the hairpin region, whereas miR529 precursors are conserved outside the hairpin region, including both the 5’ and 3’ arms. Phylogenetic analysis showed that MIR156 and MIR529 evolved independently, through divergent evolutionary patterns. The two genes also exhibit different expression patterns, with MIR529 preferentially expressed in reproductive tissues and MIR156 in other tissues. PARE analysis revealed that miR156 and miR529 possess specific targets in addition to common targets in maize, pointing to functional differences between them. Based on our findings, we developed a method for the rapid identification of miR529 and miR156 family members and uncovered the evolutionary divergence of these families, providing insights into their different regulatory roles in plant growth and development.

scholarly journals Modeling Enhancer-Promoter Interactions with Attention-Based Neural Networks

2017 ◽  
Author(s):  
Weiguang Mao ◽  
Dennis Kostka ◽  
Maria Chikina
Keyword(s):  
Dna Sequences ◽  
Target Genes ◽  
Expression Patterns ◽  
Regulatory Sequences ◽  
Learning Approaches ◽  
Interaction Prediction ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Enhancer Function ◽  
Enhancer Sequences

AbstractBackgroundGene regulatory sequences play critical roles in ensuring tightly controlled RNA expression patterns that are essential in a large variety of biological processes. Specifically, enhancer sequences drive expression of their target genes, and the availability of genome-wide maps of enhancer-promoter interactions has opened up the possibility to use machine learning approaches to extract and interpret features that define these interactions in different biological contexts.MethodsInspired by machine translation models we develop an attention-based neural network model, EPIANN, to predict enhancer-promoter interactions based on DNA sequences. Codes and data are available at https://github.com/wgmao/EPIANN.ResultsOur approach accurately predicts enhancer-promoter interactions across six cell lines. In addition, our method generates pairwise attention scores at the sequence level, which specify how short regions in the enhancer and promoter pair-up to drive the interaction prediction. This allows us to identify over-represented transcription factors (TF) binding sites and TF-pair interactions in the context of enhancer function.

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