keyword
https://read.qxmd.com/read/33287328/dna-damaged-induced-cell-death-in-oocytes
#21
REVIEW
Jakob Gebel, Marcel Tuppi, Nicole Sänger, Björn Schumacher, Volker Dötsch
The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible...
December 3, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/33202205/molecular-mechanisms-and-function-of-the-p53-protein-family-member-p73
#22
REVIEW
G Melino
Over 20 years after identification of p53 and its crucial function in cancer progression, two members of the same protein family were identified, namely p63 and p73. Since then, a body of information has been accumulated on each of these genes and their interrelations. Biological role of p73 has been elucidated thanks to four distinct knockout mice models: (i) with deletion of the entire TP73 gene, (ii) with deletion of exons encoding the full length TAp73 isoforms, (iii) with deletions of exons encoding the shorter DNp73 isoform, and (iv) with deletion of exons encoding C-terminal of the alpha isoform...
October 2020: Biochemistry. Biokhimii︠a︡
https://read.qxmd.com/read/33069756/p73-from-the-p53-shadow-to-a-major-pharmacological-target-in-anticancer-therapy
#23
JOURNAL ARTICLE
Helena Ramos, Liliana Raimundo, Lucília Saraiva
p73, along with p53 and p63, belongs to the p53 family of transcription factors. Besides the p53-like tumor suppressive activities, p73 has unique roles, namely in neuronal development and differentiation. In addition, the TP73 gene is rarely mutated in tumors. This makes p73 a highly appealing therapeutic target, particularly towards cancers with a null or disrupted p53 pathway. Distinct isoforms are transcribed from the TP73 locus either with (TAp73) and without (ΔNp73) the N-terminal transactivation domain...
October 15, 2020: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/32918225/crosstalk-between-vitamin-d-and-p53-signaling-in-cancer-an-update
#24
REVIEW
Jörg Reichrath, Sandra Reichrath, Thomas Vogt, Klaus Römer
It has now been convincingly shown that vitamin D and p53 signaling protect against spontaneous or carcinogen-induced malignant transformation of cells. The vitamin D receptor (VDR) and the p53/p63/p73 proteins (the p53 family hereafter) exert their effects as receptors/sensors that turn into transcriptional regulators upon stimulus. While the p53 clan, mostly in the nucleoplasm, responds to a large and still growing number of alterations in cellular homeostasis commonly referred to as stress, the nuclear VDR is transcriptionally activated after binding its naturally occurring biologically active ligand 1,25-dihydroxyvitamin D with high affinity...
2020: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/32917730/p63-related-signaling-at-a-glance
#25
REVIEW
Matthew L Fisher, Seamus Balinth, Alea A Mills
p63 (also known as TP63) is a transcription factor of the p53 family, along with p73. Multiple isoforms of p63 have been discovered and these have diverse functions encompassing a wide array of cell biology. p63 isoforms are implicated in lineage specification, proliferative potential, differentiation, cell death and survival, DNA damage response and metabolism. Furthermore, p63 is linked to human disease states including cancer. p63 is critical to many aspects of cell signaling, and in this Cell science at a glance article and the accompanying poster, we focus on the signaling cascades regulating TAp63 and ΔNp63 isoforms and those that are regulated by TAp63 and ΔNp63, as well the role of p63 in disease...
September 11, 2020: Journal of Cell Science
https://read.qxmd.com/read/31910062/the-p53-family-reaches-the-final-frontier-the-variegated-regulation-of-the-dark-matter-of-the-genome-by-the-p53-family-in-cancer
#26
JOURNAL ARTICLE
Marco Napoli, Elsa R Flores
The tumour suppressor p53 and its paralogues, p63 and p73, are essential to maintain cellular homoeostasis and the integrity of the cell's genetic material, thus meriting the title of 'guardians of the genome'. The p53 family members are transcription factors and fulfill their activities by controlling the expression of protein-coding and non-coding genes. Here, we review how the latter group transcended from the 'dark matter' of the transcriptome, providing unexpected and intriguing anti-cancer therapeutic strategies...
January 7, 2020: RNA Biology
https://read.qxmd.com/read/31840114/the-interplay-between-epstein-bar-virus-ebv-with-the-p53-and-its-homologs-during-ebv-associated-malignancies
#27
REVIEW
Koustav Chatterjee, Piyanki Das, Nabanita Roy Chattopadhyay, Sudipa Mal, Tathagata Choudhuri
p53, p63, and p73, the members of the p53 family of proteins, are structurally similar proteins that play central roles regulating cell cycle and apoptotic cell death. Alternative splicing at the carboxyl terminus and the utilization of different promoters further categorizes these proteins as having different isoforms for each. Among such isoforms, TA and ΔN versions of each protein serve as the pro and the anti-apoptotic proteins, respectively. Changes in the expression patterns of these isoforms are noted in many human cancers...
November 2019: Heliyon
https://read.qxmd.com/read/31817935/the-diverse-functions-of-mutant-53-its-family-members-and-isoforms-in-cancer
#28
REVIEW
Callum Hall, Patricia A J Muller
The p53 family of proteins has grown substantially over the last 40 years. It started with p53, then p63, p73, isoforms and mutants of these proteins. The function of p53 as a tumour suppressor has been thoroughly investigated, but the functions of all isoforms and mutants and the interplay between them are still poorly understood. Mutant p53 proteins lose p53 function, display dominant-negative (DN) activity and display gain-of-function (GOF) to varying degrees. GOF was originally attributed to mutant p53's inhibitory function over the p53 family members p63 and p73...
December 7, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/31712410/mutant-p53-antagonizes-p63-p73-mediated-tumor-suppression-via-notch1
#29
JOURNAL ARTICLE
Jin Zhang, Wenqiang Sun, Xiangmudong Kong, Yanhong Zhang, Hee Jung Yang, Cong Ren, Yuqian Jiang, Mingyi Chen, Xinbin Chen
p53 is the most frequently mutated gene in human cancers and mutant p53 has a gain of function (GOF) that promotes tumor progression and therapeutic resistance. One of the major GOF activities of mutant p53 is to suppress 2 other p53 family proteins, p63 and p73. However, the molecular basis is not fully understood. Here, we examined whether mutant p53 antagonizes p63/p73-mediated tumor suppression in vivo by using mutant p53-R270H knockin and TAp63/p73 -deficient mouse models. We found that knockin mutant p53-R270H shortened the life span of p73 +/- mice and subjected TAp63 +/- or p73 +/- mice to T lymphoblastic lymphomas (TLBLs)...
November 26, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/31537884/the-specific-seroreactivity-to-%C3%A2-np73-isoforms-shows-higher-diagnostic-ability-in-colorectal-cancer-patients-than-the-canonical-p73-protein
#30
JOURNAL ARTICLE
María Garranzo-Asensio, Ana Guzmán-Aránguez, Carmen Povés, María Jesús Fernández-Aceñero, Ana Montero-Calle, María Ángeles Ceron, Servando Fernandez-Diez, Nuria Rodríguez, Marta Gómez de Cedrón, Ana Ramírez de Molina, Gemma Domínguez, Rodrigo Barderas
The p53-family is tightly regulated at transcriptional level. Due to alternative splicing, up to 40 different theoretical proteoforms have been described for p73 and at least 20 and 10 for p53 and p63, respectively. However, only the canonical proteins have been evaluated as autoantibody targets in cancer patients for diagnosis. In this study, we have cloned and expressed in vitro the most upregulated proteoforms of p73, ΔNp73α and ΔNp73β, for the analysis of their seroreactivity by a developed luminescence based immunoassay test using 145 individual plasma from colorectal cancer, premalignant individuals and healthy controls...
September 19, 2019: Scientific Reports
https://read.qxmd.com/read/31448276/reciprocal-crosstalk-between-yap1-hippo-pathway-and-the-p53-family-proteins-mechanisms-and-outcomes-in-cancer
#31
REVIEW
Nitin Raj, Rakesh Bam
The YAP1/Hippo and p53 pathways are critical protectors of genome integrity in response to DNA damage. Together, these pathways secure cellular adaptation and maintain overall tissue integrity through transcriptional re-programing downstream of various environmental and biological cues generated during normal tissue growth, cell proliferation, and apoptosis. Genetic perturbations in YAP1/Hippo and p53 pathways are known to contribute to the cells' ability to turn rogue and initiate tumorigenesis. The Hippo and p53 pathways cooperate on many levels and are closely coordinated through multiple molecular components of their signaling pathways...
2019: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/31340447/molecular-mechanisms-of-p63-mediated-squamous-cancer-pathogenesis
#32
REVIEW
Michael A Moses, Andrea L George, Nozomi Sakakibara, Kanwal Mahmood, Roshini M Ponnamperuma, Kathryn E King, Wendy C Weinberg
The p63 gene is a member of the p53/p63/p73 family of transcription factors and plays a critical role in development and homeostasis of squamous epithelium. p63 is transcribed as multiple isoforms; ΔNp63α, the predominant p63 isoform in stratified squamous epithelium, is localized to the basal cells and is overexpressed in squamous cell cancers of multiple organ sites, including skin, head and neck, and lung. Further, p63 is considered a stem cell marker, and within the epidermis, ΔNp63α directs lineage commitment...
July 23, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/31336860/gliotoxin-enhances-autophagic-cell-death-via-the-dapk1-tap63-signaling-pathway-in-paclitaxel-resistant-ovarian-cancer-cells
#33
JOURNAL ARTICLE
Ga-Bin Park, Jee-Yeong Jeong, Daejin Kim
Death-associated protein kinase 1 (DAPK1) expression induced by diverse death stimuli mediates apoptotic activity in various cancers, including ovarian cancer. In addition, mutual interaction between the tumor suppressor p53 and DAPK1 influences survival and death in several cancer cell lines. However, the exact role and connection of DAPK1 and p53 family proteins (p53, p63, and p73) in drug-resistant ovarian cancer cells have not been studied previously. In this study, we investigated whether DAPK1 induction by gliotoxin derived from marine fungus regulates the level of transcriptionally active p63 (TAp63) to promote apoptosis in an autophagy-dependent manner...
July 12, 2019: Marine Drugs
https://read.qxmd.com/read/31295913/platinum-salts-in-patients-with-breast-cancer-a-focus-on-predictive-factors
#34
REVIEW
Mattia Garutti, Giacomo Pelizzari, Michele Bartoletti, Matilde Clarissa Malfatti, Lorenzo Gerratana, Gianluca Tell, Fabio Puglisi
Breast cancer (BC) is the most frequent oncologic cause of death among women and the improvement of its treatments is compelling. Platinum salts (e.g., carboplatin, cisplatin, and oxaliplatin) are old drugs still used to treat BC, especially the triple-negative subgroup. However, only a subset of patients see a concrete benefit from these drugs, raising the question of how to select them properly. Therefore, predictive biomarkers for platinum salts in BC still represent an unmet clinical need. Here, we review clinical and preclinical works in order to summarize the current evidence about predictive or putative platinum salt biomarkers in BC...
July 10, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/31286584/intersection-of-the-p63-and-nf-%C3%AE%C2%BAb-pathways-in-epithelial-homeostasis-and-disease
#35
JOURNAL ARTICLE
Kathryn E King, Andrea L George, Nozomi Sakakibara, Kanwal Mahmood, Michael A Moses, Wendy C Weinberg
Overexpression of ΔNp63α, a member of the p53/p63/p73 family of transcription factors, is a molecular attribute of human squamous cancers of the head and neck, lung and skin. The TP63 gene plays important roles in epidermal morphogenesis and homeostasis, regulating diverse biological processes including epidermal fate decisions and keratinocyte proliferation and survival. When overexpressed experimentally in primary mouse keratinocytes, ΔNp63α maintains a basal cell phenotype including the loss of normal calcium-mediated growth arrest, at least in part through the activation and enhanced nuclear accumulation of the c-rel subunit of NF-κB (Nuclear Factor-kappa B)...
July 8, 2019: Molecular Carcinogenesis
https://read.qxmd.com/read/31258748/role-of-p53-family-proteins-in-metformin-anti-cancer-activities
#36
REVIEW
Yong Yi, Wenhua Zhang, Jianqiao Yi, Zhi-Xiong Xiao
Metformin has been used as therapy for type 2 diabetes for many years. Clinical and basic evidence as indicated that metformin has anti-cancer activities. It has been well-established that metformin activates AMP-activated protein kinase (AMPK), which in turn regulates energy homeostasis. However, the mechanistic aspects of metformin anti-cancer activity remain elusive. p53 family proteins, including p53, p63 and p73, have diverse biological functions, including regulation of cell growth, survival, development, senescence and aging...
2019: Journal of Cancer
https://read.qxmd.com/read/30886745/protoporphyrin-ix-is-a-dual-inhibitor-of-p53-mdm2-and-p53-mdm4-interactions-and-induces-apoptosis-in-b-cell-chronic-lymphocytic-leukemia-cells
#37
JOURNAL ARTICLE
Liren Jiang, Natasha Malik, Pilar Acedo, Joanna Zawacka-Pankau
p53 is a tumor suppressor, which belongs to the p53 family of proteins. The family consists of p53, p63 and p73 proteins, which share similar structure and function. Activation of wild-type p53 or TAp73 in tumors leads to tumor regression, and small molecules restoring the p53 pathway are in clinical development. Protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid, is a clinically approved drug applied in photodynamic diagnosis and therapy. PpIX induces p53-dependent and TAp73-dependent apoptosis and inhibits TAp73/MDM2 and TAp73/MDM4 interactions...
2019: Cell Death Discovery
https://read.qxmd.com/read/30861992/preventive-effect-of-lactobacillus-fermentum-cqpc08-on-4-nitroquineline-1-oxide-induced-tongue-cancer-in-c57bl-6-mice
#38
JOURNAL ARTICLE
Bihui Liu, Jing Zhang, Ruokun Yi, Xianrong Zhou, Xingyao Long, Yanni Pan, Xin Zhao
Lactobacillus fermentum CQPC08 (LF-CQPC08) is a newly discovered strain of bacteria isolated and identified from traditional pickled vegetables in Sichuan, China. We used 4-nitroquinoline 1-oxide to establish an experimental tongue cancer mouse model to evaluate the preventive effect of LF-CQPC08 on tongue cancer in vivo. Lactobacillus delbruechii subsp. bulgaricus , is a common commercial strain and is used as a positive control to compare the effect with LF-CQPC08. The preventive strength and mechanism of LF-CQPC08 on tongue cancer were determined by measuring the biochemical indicators in mouse serum and tissues...
March 11, 2019: Foods (Basel, Switzerland)
https://read.qxmd.com/read/30735716/the-c-terminal-sam-domain-of-p73-binds-to-the-n-terminus-of-mdm2
#39
JOURNAL ARTICLE
José L Neira, Clara Díaz-García, Manuel Prieto, Ana Coutinho
BACKGROUND: The p53, p63 and p73 proteins belong to the p53 family of transcription factors, playing key roles in tumour suppression. The α-splice variant of p73 (p73α) has at its C terminus a sterile alpha motif (SAM); this domain, SAMp73, formed by five helices (α1 to α5), is thought to mediate in protein-protein interactions. The E3-ligase MDM2 binds to p73 at its N terminus transactivation domain (TA), but it does not promote its degradation via ubiquitination; however, the details of such MDM2/p73 interaction are not fully known...
February 5, 2019: Biochimica et Biophysica Acta. General Subjects
https://read.qxmd.com/read/30700826/synergistic-activation-of-the-neu4-promoter-by-p73-and-ap2-in-colon-cancer-cells
#40
JOURNAL ARTICLE
Bi-He Cai, Po-Han Wu, Chi-Kan Chou, Hsiang-Chi Huang, Chia-Chun Chao, Hsiao-Yu Chung, Hsueh-Yi Lee, Jang-Yi Chen, Reiji Kannagi
More than 50% of colon cancers bear mutations in p53, one of the most important tumor suppressors, and its family members p63 or p73 are expected to contribute to inhibiting the progression of colon cancers. The AP2 family also acts as a tumor suppressor. Here we found that p73 and AP2 are able to activate NEU4, a neuraminidase gene, which removes the terminal sialic acid residues from cancer-associated glycans. Under serum starvation, NEU4 was up-regulated and one of the NEU4 target glycans, sialyl Lewis X, was decreased, whereas p73 and AP2 were up-regulated...
January 30, 2019: Scientific Reports
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