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P53 p63 p73 cancer

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https://www.readbyqxmd.com/read/29878773/binding-kinetics-of-the-intrinsically-disordered-p53-family-transactivation-domains-and-mdm2
#1
Emma Åberg, O Andreas Karlsson, Eva Andersson, Per Jemth
Because of their prominent roles in cell cycle regulation and cancer the interaction between MDM2 and the intrinsically disordered transactivation domain (TAD) of p53 is exceptionally well studied. However, while there are numerous computational studies on the interaction mechanism there is a paucity of experimental data regarding the kinetics and mechanism. We have used stopped flow fluorescence to investigate the binding reaction between MDM2 and the TAD from p53 as well as from its paralogs p63 and p73, and in particular focussed on the salt dependence of the interaction...
June 7, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29662640/potential-therapeutic-targets-of-tp53-gene-in-the-context-of-its-classically-canonical-functions-and-its-latest-non-canonical-functions-in-human-cancer
#2
REVIEW
Toshimichi Tanaka, Masahiko Watanabe, Keishi Yamashita
In normal tissue, p53 protein has a wide range of functions involving cell homeostasis; its mutation, however, permits a carcinogenic acquisition of function. TP53 gene mutation is a major genomic aberration in various human cancers and is a critical event in the multi-step carcinogenesis process. TP53 mutation is clinically relevant for the molecular classification of carcinogenesis, as most recently described rigorously by the Cancer Genome Atlas Research Network. TP53 gene mutation has been considered to work as a tumor suppressor gene through the loss of its transcriptional activity, which is designated as a canonical function...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29518025/emerging-roles-of-p53-family-members-in-glucose-metabolism
#3
REVIEW
Yoko Itahana, Koji Itahana
Glucose is the key source for most organisms to provide energy, as well as the key source for metabolites to generate building blocks in cells. The deregulation of glucose homeostasis occurs in various diseases, including the enhanced aerobic glycolysis that is observed in cancers, and insulin resistance in diabetes. Although p53 is thought to suppress tumorigenesis primarily by inducing cell cycle arrest, apoptosis, and senescence in response to stress, the non-canonical functions of p53 in cellular energy homeostasis and metabolism are also emerging as critical factors for tumor suppression...
March 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29339502/protein-aggregation-of-the-p63-transcription-factor-underlies-severe-skin-fragility-in-aec-syndrome
#4
Claudia Russo, Christian Osterburg, Anna Sirico, Dario Antonini, Raffaele Ambrosio, Julia Maren Würz, Jörg Rinnenthal, Marco Ferniani, Sebastian Kehrloesser, Birgit Schäfer, Peter Güntert, Satrajit Sinha, Volker Dötsch, Caterina Missero
The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29260852/targeting-the-prion-like-aggregation-of-mutant-p53-to-combat-cancer
#5
Jerson L Silva, Elio A Cino, Iaci N Soares, Vitor F Ferreira, Guilherme A P de Oliveira
Prion-like behavior of several amyloidogenic proteins has been demonstrated in recent years. Despite having functional roles in some cases, irregular aggregation can have devastating consequences. The most commonly known amyloid diseases are Alzheimer's, Parkinson's, and Transmissible Spongiform Encephalopathies (TSEs). The pathophysiology of prion-like diseases involves the structural transformation of wild-type (wt) proteins to transmissible forms that can convert healthy proteins, generating aggregates. The mutant form of tumor suppressor protein, p53, has recently been shown to exhibit prion-like properties...
January 16, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29156626/surface-plasmon-resonance-sensing-of-biorecognition-interactions-within-the-tumor-suppressor-p53-network
#6
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
#7
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...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29077094/non-oncogenic-roles-of-tap73-from-multiciliogenesis-to-metabolism
#8
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
#9
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
#10
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...
December 2017: Cancer Science
https://www.readbyqxmd.com/read/28984872/p53-shades-of-hippo
#11
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...
January 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28915717/p53-p63-and-p73-in-the-wonderland-of-s-cerevisiae
#12
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
#13
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
#14
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
#15
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 among the family members...
July 1, 2018: 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
#16
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
#17
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...
December 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
#18
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
#19
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
#20
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)2 D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2 D3 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)2 D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
September 15, 2017: Molecular and Cellular Endocrinology
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