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P53 p63 p73 cancer

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https://www.readbyqxmd.com/read/29156626/surface-plasmon-resonance-sensing-of-biorecognition-interactions-within-the-tumor-suppressor-p53-network
#1
REVIEW
Ilaria Moscetti, Salvatore Cannistraro, Anna Rita Bizzarri
Surface Plasmon Resonance (SPR) is a powerful technique to study the kinetics of biomolecules undergoing biorecognition processes, particularly suited for protein-protein interactions of biomedical interest. The potentiality of SPR was exploited to sense the interactions occurring within the network of the tumor suppressor p53, which is crucial for maintaining genome integrity and whose function is inactivated, mainly by down regulation or by mutation, in the majority of human tumors. This study includes p53 down-regulators, p53 mutants and also the p53 family members, p63 and p73, which could vicariate p53 protective function...
November 20, 2017: Sensors
https://www.readbyqxmd.com/read/29107083/p63-and-p73-repress-cxcr5-chemokine-receptor-gene-expression-in-p53-deficient-mcf-7-breast-cancer-cells-during-genotoxic-stress
#2
Nikita A Mitkin, Alisa M Muratova, George V Sharonov, Kirill V Korneev, Ekaterina N Sviriaeva, Dmitriy Mazurov, Anton M Schwartz, Dmitry V Kuprash
Many types of chemotherapeutic agents induce of DNA-damage that is accompanied by activation of p53 tumor suppressor, a key regulator of tumor development and progression. In our previous study we demonstrated that p53 could repress CXCR5 chemokine receptor gene in MCF-7 breast cancer cells via attenuation of NFkB activity. In this work we aimed to determine individual roles of p53 family members in the regulation of CXCR5 gene expression under genotoxic stress. DNA-alkylating agent methyl methanesulfonate caused a reduction in CXCR5 expression not only in parental MCF-7 cells but also in MCF-7-p53off cells with CRISPR/Cas9-mediated inactivation of the p53 gene...
November 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29077094/non-oncogenic-roles-of-tap73-from-multiciliogenesis-to-metabolism
#3
REVIEW
Alice Nemajerova, Ivano Amelio, Jakob Gebel, Volker Dötsch, Gerry Melino, Ute M Moll
The p53 family of transcription factors (p53, p63 and p73) covers a wide range of functions critical for development, homeostasis and health of mammals across their lifespan. Beside the well-established tumor suppressor role, recent evidence has highlighted novel non-oncogenic functions exerted by p73. In particular, p73 is required for multiciliated cell (MCC) differentiation; MCCs have critical roles in brain and airways to move fluids across epithelial surfaces and to transport germ cells in the reproductive tract...
October 27, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29065514/the-role-of-mdm2-in-promoting-genome-stability-versus-instability
#4
REVIEW
M Reza Saadatzadeh, Adily N Elmi, Pankita H Pandya, Khadijeh Bijangi-Vishehsaraei, Jixin Ding, Christopher W Stamatkin, Aaron A Cohen-Gadol, Karen E Pollok
In cancer, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The impact of MDM2 on cell survival versus cell death is complex and dependent on levels of MDM2 isoforms, p53 status, and cellular context. Extensive investigations have demonstrated that MDM2 protein-protein interactions with p53 and other p53 family members (p63 and p73) block their ability to function as transcription factors that regulate cell growth and survival...
October 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29030916/identification-and-characterization-of-a-metastatic-suppressor-brms1l-as-a-target-gene-of-p53
#5
Ryota Koyama, Miyuki Tamura, Takafumi Nakagaki, Tomoko Ohashi, Masashi Idogawa, Hiromu Suzuki, Takashi Tokino, Yasushi Sasaki
The tumor suppressor p53 and its family members, p63 and p73, play a pivotal role in the cell fate determination in response to diverse upstream signals. As transcription factors, p53 family proteins regulate a number of genes that are involved in cell-cycle arrest, apoptosis, senescence, and maintenance of genomic stability. Recent studies revealed that p53 family proteins are important for the regulation of cell invasion and migration. Microarray analysis showed that breast cancer metastasis-suppressor 1- like (BRMS1L) is upregulated by p53 family proteins, specifically p53, TAp63γ, and TAp73β...
October 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28984872/p53-shades-of-hippo
#6
Noa Furth, Yael Aylon, Moshe Oren
The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28915717/p53-p63-and-p73-in-the-wonderland-of-s-cerevisiae
#7
REVIEW
Olivier Billant, Marc Blondel, Cécile Voisset
Since its discovery in 1979, p53 has been on the forefront of cancer research. It is considered a master gene of cancer suppression and is found mutated in around 50% of all human tumors. In addition, the progressive identification of p53-related transcription factors p63 and p73 as well as their multiple isoforms have added further layers of complexity to an already dense network. Among the numerous models used to unravel the p53 family mysteries, S. cerevisiae has been particularly useful. This seemingly naive model allows the expression of a functional human p53 and thus the assessment of p53 intrinsic transcriptional activity...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28827783/ccdc3-a-new-p63-target-involved-in-regulation-of-liver-lipid-metabolism
#8
Wenjuan Liao, Hongbing Liu, Yiwei Zhang, Ji Hoon Jung, Jiaxiang Chen, Xiaohua Su, Yeong C Kim, Elsa R Flores, San Ming Wang, Malwina Czarny-Ratajczak, Wen Li, Shelya X Zeng, Hua Lu
TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794013/control-mechanisms-in-germ-cells-mediated-by-p53-family-proteins
#9
REVIEW
Jakob Gebel, Marcel Tuppi, Katharina Krauskopf, Daniel Coutandin, Susanne Pitzius, Sebastian Kehrloesser, Christian Osterburg, Volker Dötsch
Germ cells are totipotent and, in principle, immortal as they are the source for new germ cells in each generation. This very special role requires tight quality control systems. The p53 protein family constitutes one of the most important quality surveillance systems in cells. Whereas p53 has become famous for its role as the guardian of the genome in its function as the most important somatic tumor suppressor, p63 has been nicknamed 'guardian of the female germ line'. p63 is strongly expressed in resting oocytes and responsible for eliminating those that carry DNA double-strand breaks...
August 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28793777/the-p53-family-in-brain-disease
#10
Massimiliano Agostini, Gerry Melino, Francesca Bernassola
SIGNIFICANCE: The p53 family of transcription factors, including p53, p63 and p73, plays key roles in both biological and pathological processes, including cancer and neural development. Recent Advances: In recent years, a growing body of evidence has indicated that the entire p53 family is involved in the regulation of the central nervous system (CNS) functions as well as in the pathogenesis of several neurological disorders. Mechanistically, the p53 proteins control neuronal cell fate, terminal differentiation and survival, via a complex interplay amongst the family members...
August 10, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28697449/binding-kinetics-of-mutant-p53r175h-with-wild-type-p53-and-p63-a-surface-plasmon-resonance-and-atomic-force-spectroscopy-study
#11
Ilaria Moscetti, Anna Rita Bizzarri, Salvatore Cannistraro
The oncogenic mutant p53R175H, one of the most frequently occurring in human cancers and usually associated with poor prognosis and chemo resistance, can exert a dominant negative effect over p53 family members, namely wild type p53, p63 and p73, inhibiting their oncosuppressive function. Novel anticancer strategies based on drugs able to prevent the formation of complexes between p53R175H and the p53 family members call for a deeper knowledge on the molecular mechanisms of their interaction. To this aim, p53R175H/p63 and p53R175H/p53 complexes were investigated in vitro by using Surface Plasmon Resonance and Atomic Force Spectroscopy, two emerging and complementary techniques able to provide interaction kinetic information, in near physiological conditions and without any labelling...
September 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28690024/the-p53-gene-with-emphasis-on-its-paralogues-in-mosquitoes
#12
REVIEW
Tien-Huang Chen, Yi-Jun Wu, Jiun-Nan Hou, Cheng-Hsun Chiu, Wei-June Chen
The p53 gene is highly important in human cancers, as it serves as a tumor-suppressor gene. Subsequently, two p53 homologues, i.e., p73 and p63, with high identity of amino acids were identified, leading to construction of the p53 family. The p53 gene is highly important in human cancer because it usually transcribes genes that function by causing apoptosis in mammalian cells. In contrast, p63 and p73 tend to be more important in modulating development than inducing cell death, even though they share similar protein structures...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28654906/p53-p63-and-p73-in-the-wonderland-of-s-cerevisiae
#13
REVIEW
Olivier Billant, Marc Blondel, Cécile Voisset
Since its discovery in 1979, p53 has been on the forefront of cancer research. It is considered a master gene of cancer suppression and is found mutated in around 50% of all human tumors. In addition, the progressive identification of p53-related transcription factors p63 and p73 as well as their multiple isoforms have added further layers of complexity to an already dense network. Among the numerous models used to unravel the p53 family mysteries, S. cerevisiae has been particularly useful. This seemingly naive model allows the expression of a functional human p53 and thus the assessment of p53 intrinsic transcriptional activity...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635633/new-insights-in-thyroid-cancer-and-p53-family-proteins
#14
REVIEW
Livia Manzella, Stefania Stella, Maria Stella Pennisi, Elena Tirrò, Michele Massimino, Chiara Romano, Adriana Puma, Martina Tavarelli, Paolo Vigneri
Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#15
REVIEW
Jörg Reichrath, Roman Saternus, Thomas Vogt
The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)2D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2D3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)2D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
May 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28471195/-application-of-pla-method-for-detection-of-p53-p63-p73-complexes-in-situ-in-tumour-cells-and-tumour-tissue
#16
V Hrabal, M Nekulová, R Nenutil, J Holčaková, P J Coates, B Vojtěšek
BACKGROUND: PLA (proximity ligation assay) can be used for detection of protein-protein interactions in situ directly in cells and tissues. Due to its high sensitivity and specificity it is useful for detection, localization and quantification of protein complexes with single molecule resolution. One of the mechanisms of mutated p53 gain of function is formation of proten-protein complexes with other members of p53 family - p63 and p73. These interactions influences chemosensitivity and invasivity of cancer cells and this is why these complexes are potential targets of anti-cancer therapy...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28439015/mutant-p53-perturbs-dna-replication-checkpoint-control-through-topbp1-and-treslin
#17
Kang Liu, Fang-Tsyr Lin, Joshua D Graves, Yu-Ju Lee, Weei-Chin Lin
Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28211873/the-p53-family-members-have-distinct-roles-during-mammalian-embryonic-development
#18
Jeanine L Van Nostrand, Margot E Bowen, Hannes Vogel, Maria Barna, Laura D Attardi
The p53 tumor suppressor is a member of a multi-protein family, including the p63 and p73 transcription factors. These proteins can bind to the same consensus sites in DNA and activate the same target genes, suggesting that there could be functional redundancy between them. Indeed, double mutant mice heterozygous for any two family member-encoding genes display enhanced cancer phenotypes relative to single heterozygous mutants. However, whether the family members play redundant roles during embryonic development has remained largely unexplored...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27884017/the-p53-family-orchestrates-the-regulation-of-metabolism-physiological-regulation-and-implications-for-cancer-therapy
#19
REVIEW
Marco Napoli, Elsa R Flores
The p53 family of transcription factors is essential to counteract tumour formation and progression. Although previously this was exclusively associated with the ability of the p53 family to induce cell cycle arrest and apoptosis, an increasing number of reports have now indisputably demonstrated that the tumour suppressive functions of the p53 family members also rely on their ability to control and regulate cellular metabolism and maintain cellular oxidative homeostasis. Here, we review how each p53 family member, including p63 and p73, controls metabolic pathways in physiological conditions, and how these mechanisms could be exploited to provide anticancer therapeutic opportunities...
January 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/27600721/aggregation-tendencies-in-the-p53-family-are-modulated-by-backbone-hydrogen-bonds
#20
Elio A Cino, Iaci N Soares, Murilo M Pedrote, Guilherme A P de Oliveira, Jerson L Silva
The p53 family of proteins is comprised of p53, p63 and p73. Because the p53 DNA binding domain (DBD) is naturally unstable and possesses an amyloidogenic sequence, it is prone to form amyloid fibrils, causing loss of functions. To develop p53 therapies, it is necessary to understand the molecular basis of p53 instability and aggregation. Light scattering, thioflavin T (ThT) and high hydrostatic pressure (HHP) assays showed that p53 DBD aggregates faster and to a greater extent than p63 and p73 DBDs, and was more susceptible to denaturation...
2016: Scientific Reports
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