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TAp73

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https://www.readbyqxmd.com/read/29733853/p73-alternative-splicing-exploring-a-biological-role-for-the-c-terminal-isoforms
#1
REVIEW
Polina Vikhreva, Gerry Melino, Ivano Amelio
p73 (encoded by TP73 gene) is a p53 related protein that functions as a transcriptional factor. Similarly to p53, following DNA damage, p73 is stabilised, activated and controls expression of target genes that are involved in the regulation of cycle arrest and apoptosis. However great complexity to the function of this gene is given by the wide range of its non-tumour related roles, which include neurological development, ciliogenesis and fertility. From the structural point of view, p73 displays an intricate range of regulations because it can be expressed both as a N-terminally deleted dominant-negative isoforms and as multiple alternatively spliced C-terminal isoforms, that can include or not a sterile alfa motif (SAM) domain...
May 4, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29702195/hedgehog-signaling-negatively-co-regulates-bh3-only-protein-noxa-and-tap73-in-tp53-mutated-cells
#2
Michael Torsten Meister, Cathinka Boedicker, Thomas Klingebiel, Simone Fulda
In the present study, we show that pharmacological repression by the Hedgehog (Hh) pathway inhibitor (HPI) GANT61 induces expression of the proapoptotic protein Noxa in TP53-mutated embryonal pediatric tumor cells driven by Hh signaling (i.e. rhabdomyosarcoma (RMS) and medulloblastoma (MB)). Similarly, genetic silencing of Gli1 by siRNA causes increased Noxa mRNA and protein levels, while overexpression of Gli1 results in decreased Noxa expression. Furthermore, TAp73 mRNA and protein levels are increased upon Gli1 knockdown, while Gli1 overexpression reduces TAp73 mRNA and protein levels...
April 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29620279/impact-of-runx2-gene-silencing-on-the-gemcitabine-sensitivity-of-p53%C3%A2-mutated-pancreatic-cancer-miapaca%C3%A2-2-spheres
#3
Meijie Sang, Mizuyo Nakamura, Takehiro Ogata, Dan Sun, Osamu Shimozato, Toshio Nikaido, Toshinori Ozaki
Recently, it has been well‑recognized that the response toward anticancer drugs differs between two‑ and three‑dimensional (2D and 3D) in vitro cancer cell growth models. In the present study, we have demonstrated that, similar to the conventional 2D monolayer culture systems which often lack in vivo physiological insights, RUNX2 gene silencing increases the gemcitabine (GEM) sensitivity of the 3D spheres generated from p53‑mutated pancreatic cancer MiaPaCa‑2 cells. According to our results, MiaPaCa‑2 cells, but not p53‑wild‑type pancreatic cancer SW1990 cells efficiently formed sphere structures in serum‑free sphere‑forming medium...
March 30, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29558908/impact-of-runx2-on-drug-resistant-human-pancreatic-cancer-cells-with-p53-mutations
#4
REVIEW
Toshinori Ozaki, Meng Yu, Danjing Yin, Dan Sun, Yuyan Zhu, Youquan Bu, Meixiang Sang
BACKGROUND: Despite the remarkable advances in the early diagnosis and treatment, overall 5-year survival rate of patients with pancreatic cancer is less than 10%. Gemcitabine (GEM), a cytidine nucleoside analogue and ribonucleotide reductase inhibitor, is a primary option for patients with advanced pancreatic cancer; however, its clinical efficacy is extremely limited. This unfavorable clinical outcome of pancreatic cancer patients is at least in part attributable to their poor response to anti-cancer drugs such as GEM...
March 20, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29552154/association-between-tap73-p53-and-vash1-expression-in-lung-adenocarcinoma
#5
Meng Wu, Zhihua Zhang, Fangxu Ma, Xiulong Zhang, Zhilin Zhang, Jianhua Tang, Ping Chen, Chunyan Zhou, Weiping Wang
TAp73 and p53 are involved in regulating tumor angiogenesis and vasohibin-1 (VASH1) is an anti-angiogenic factor. Whether TAp73 regulates angiogenesis positively or negatively is controversial. The status of P53 may determine the effect of TAp73 on angiogenesis. To the best of our knowledge it has not been previously reported whether TAp73, p53 and VASH1 are coexpressed in lung cancer. We profiled the association between TAp73 and p53 and VASH1 expression in lung adenocarcinoma (LAC) and investigated the function of TAp73 in regulating tumor angiogenesis...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29508625/reactive-nitrogen-species-control-apoptosis-and-autophagy-in-k562-cells-implication-of-tap73%C3%AE-induction-in-controlling-autophagy
#6
Sampurna Datta, Subhamoy Chakraborty, Chiranjit Panja, Sanjay Ghosh
The biological outcome of nitric oxide (NO) and reactive nitrogen species (RNS) in regulating pro survival and pro death autophagic pathways still demand further investigation. In the present study, we investigated the effect of nitrosative stress in K562 cells using NO donor compound DETA-NONOate, peroxynitrite, and SIN-1. Exposure to NO, peroxynitrite, and SIN-1 caused decrease in K562 cell survival. NO induced autophagy but not apoptosis or necrosis in K562 cells. In contrast, peroxynitrite and SIN-1 treatment induced apoptosis in K562 cells...
March 23, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29467540/identification-of-a-novel-microrna-mrna-regulatory-biomodule-in-human-prostate-cancer
#7
Yanqiong Zhang, Funeng Jiang, Huichan He, Jianheng Ye, Xia Mao, Qiuyan Guo, Shu-Lin Wu, Weide Zhong, Chin-Lee Wu, Na Lin
Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA-mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29452959/differential-expressions-of-mdm2-and-tap73-in-cancer-and-cancer-adjacent-tissues-in-patients-with-non-small-cell-lung-carcinoma
#8
B Wang, X Liu, H Liu, J Guo, T Zhang, N Zhou, Y Ma, H Yu, L Chen, Z Ren, K Fan, X Tian
AIM: To investigate the differences in mRNA and protein expressions of MDM2 (mouse double minute 2 homolog) and P73 in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma (NSCLC). MATERIALS AND METHODS: We compared the protein expressions of MDM2 and P73 in lung cancer and cancer-adjacent tissues in NSCLC patients by IHC (immunohistochemistry) and WB (Western blot). We divided the NSCLC patients into two subgroups, adenocarcinoma and squamous carcinoma...
February 13, 2018: Pulmonology
https://www.readbyqxmd.com/read/29434772/transcription-activated-p73-modulated-cyclin-d1-expression-leads-to-doxorubicin-resistance-in-gastric-cancer
#9
Zhi-Peng Ji, Ling Qiang, Jian-Liang Zhang
Gastric cancer (GC) is one of the leading types of cancer in terms of mortality cases worldwide. Doxorubicin (Dox), a common chemotherapy drug, is frequently used to treat GC; however, acquired resistance to Dox hinders the chemotherapeutic outcome and causes shorter survival in GC patients. Several Dox-resistant GC cell lines, including SGC7901, SNU-1 and SNU-5 were generated to investigate the mechanism of Dox resistance in GC. Various methods were used to test the response of Dox-resistant GC cells and parental cells, including flow cytometry, Cell Counting kit-8 assay, reverse transcription polymerase chain reaction and western blot analysis...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29362023/expression-of-tap73%C3%AE-affects-the-therapy-effect-of-chemotherapy-drugs-in-gastric-cancer
#10
Ling Qiang, ZhiPeng Ji, Xiuwen Wang
The transcription factor TAp73, a transcriptionally active isoform of p73, has high structure and function similaritieswith its homolog p53, therefore, are thought to be a cancer therapy candidate target. However, there is still a controversy about the tumor suppressor role of TAp73, since it has been found in numerous studies that TAp73 expression is elevated in different cancers. Thus, we take effort to clarify the influence of TAp73 on gastric cancer (GC) chemotherapy. Multiple cell lines of GC such as SNU-1, SNU-3, and AGS were applied to investigate expression of TAp73...
January 23, 2018: Oncology Research
https://www.readbyqxmd.com/read/29233040/integrin-%C3%AE-4-is-a-novel-transcriptional-target-of-tap73
#11
Ningxia Xie, Polina Vikhreva, Margherita Annicchiarico-Petruzzelli, Ivano Amelio, Nicolai Barlev, Richard A Knight, Gerry Melino
As a member of p53 family, p73 has attracted intense investigations due to its structural and functional similarities to p53. Among more than ten p73 variants, the transactivation (TA) domain-containing isoform TAp73 is the one that imitates the p53's behavior most. TAp73 induces apoptosis and cell cycle arrest, which endows it the capacity of tumour suppression. Also, it can exert diverse biological influences on cells through activating a complex and context dependent transcriptional programme. The transcriptional activities further broaden its roles in more intricate biological processes...
February 8, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29222041/tap73-inhibits-cell-invasion-and-migration-by-directly-activating-kai1-expression-in-colorectal-carcinoma
#12
Woo-Kyun Bae, Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Ji-Hee Lee, Keunsoo Kang, Kyung-Hyun Ryu, Hyun-Jeong Shim, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung
p73 is a member of the p53 family of transcription factors and, like p53, plays a role as a tumor suppressor. p73 is involved in development, proliferation, apoptosis and metastasis. However, the precise molecular mechanisms underlying its function in inhibiting metastasis remain largely unknown. Here, we show that induction of TAp73 decreased invasion and migration activity of colorectal cancer cells, whereas knockdown of TAp73 led to increased invasion and migration activity. KAI1 was identified as a transcriptional target of TAp73 and its expression is indispensable for TAp73-mediated inhibition of cell invasion and migration...
February 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29077094/non-oncogenic-roles-of-tap73-from-multiciliogenesis-to-metabolism
#13
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/28982757/another-case-for-diet-restriction-tap73-expressing-medulloblastomas-are-stunted-by-glutamine-withdrawal
#14
REVIEW
Marco Napoli, Elsa R Flores
Medulloblastomas are among the most common malignant brain cancers in the pediatric population and consist of at least four distinct subgroups with unique molecular and genetic features and clinical outcomes. In this issue of Genes & Development , Niklison-Chirou and colleagues (pp. 1738-1753) identify the p53 family member and p73 isoform TAp73 as a crucial factor causing glutamine addiction in aggressive medulloblastomas. Their findings pave the way for the use of glutamine restriction as an adjuvant treatment for TAp73-expressing medulloblastomas...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28978663/distinct-tp73-dapk2-atg5-pathway-involvement-in-ato-mediated-cell-death-versus-atra-mediated-autophagy-responses-in-apl
#15
Magali Humbert, Elena A Federzoni, Mario P Tschan
We have previously demonstrated that the death-associated protein kinase 2 (DAPK2) expression is significantly reduced in acute myeloid leukemia (AML), particularly in acute promyelocytic leukemia (APL) blast cells. In this study, we aimed at further understanding DAPK2 function and regulation during arsenic trioxide (ATO) cytotoxic or all-trans retinoic acid (ATRA) differentiation therapy in APL cells. We found that the p53 family member transactivation domain-p73 isoform (TAp73) binds to and activates the DAPK2 promoter, whereas the dominant-negative ΔNp73 isoform inhibits DAPK2 transcription...
December 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28971956/tap73-is-a-marker-of-glutamine-addiction-in-medulloblastoma
#16
Maria Victoria Niklison-Chirou, Ida Erngren, Mikael Engskog, Jakob Haglöf, Daniel Picard, Marc Remke, Phelim Hugh Redmond McPolin, Matthew Selby, Daniel Williamson, Steven C Clifford, David Michod, Michalis Hadjiandreou, Torbjörn Arvidsson, Curt Pettersson, Gerry Melino, Silvia Marino
Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28915954/do-some-epithelial-ovarian-cancers-originate-from-a-fallopian-tube-ciliate-cell-lineage
#17
Jan Rohozinski, Conception Diaz-Arrastia, Creighton L Edwards
There is a general agreement that a large subpopulation of serous ovarian cancers arise from the fallopian tube mucosal epithelium. However, there is still some debate as to whether the cancers originate from a secretory or ciliate cell lineage. One well established method for determining the origin of a cell line is to document the expression of genes and proteins that are cell type specific. Lineage or tissue specific patterns of gene expression are evidence of direct decent from a given cell type within a tissue...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28710427/the-essential-role-of-tap73-in-bortezomib-induced-apoptosis-in-p53-deficient-colorectal-cancer-cells
#18
Yasamin Dabiri, Sara Kalman, Clara-Marie Gürth, Jee Young Kim, Viola Mayer, Xinlai Cheng
Mutations in the tumor suppressor p53 are among the most highly occurring events in colorectal cancer (CRC). Such mutations have been shown to influence the sensitivity of cancer cells to chemotherapeutic agents. However their impact on the efficacy of the proteasomal inhibitor bortezomib remains controversial. We thus re-evaluated the toxicity of bortezomib in the CRC cell lines HCT116 wt (wild-type) and its p53-/- clone. Transient resistance to bortezomib treatment was observed in p53-null cells that was later accompanied by an increase in levels and nuclear translocation of TAp73, an isoform of the p53-homologue p73, as well as induction of apoptosis...
July 14, 2017: Scientific Reports
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
#19
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/28350813/role-of-p63-and-p73-isoforms-on-the-cell-death-in-patients-with-hepatocellular-carcinoma-submitted-to-orthotopic-liver-transplantation
#20
Raúl González, Ángel J De la Rosa, Alessandro Rufini, María A Rodríguez-Hernández, Elena Navarro-Villarán, Trinidad Marchal, Sheila Pereira, Manuel De la Mata, Martina Müller-Schilling, Juan M Pascasio-Acevedo, María T Ferrer-Ríos, Miguel A Gómez-Bravo, Francisco J Padillo, Jordi Muntané
BACKGROUND & AIMS: Patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT) have a variable 5-year survival rate limited mostly by tumor recurrence. The etiology, age, sex, alcohol, Child-Pugh, and the immunesuppressor have been associated with tumour recurrence. The expression of ΔNp73 is related to the reduced survival of patients with HCC. The study evaluated the expression of p63 and p73 isoforms and cell death receptors, and their relation to tumour recurrence and survival...
2017: PloS One
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