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p53 family member

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https://www.readbyqxmd.com/read/28794999/modulation-of-the-p53-family-network-by-rna-binding-proteins
#1
Chris Lucchesi, Jin Zhang, Xinbin Chen
Since its discovery more than three decades ago, tumor suppressor p53 has been shown to play pivotal roles in both maintaining genomic integrity and tumor suppression. p53 functions as a transcription factor responding to a multitude of cellular stressors, regulating the transcription of many genes involved in cell-cycle arrest, senescence, autophagy, and apoptosis. Extensive work has revealed that p53 is one of the most commonly mutated tumor suppressor genes. The last three decades have demonstrated that p53 activity is controlled through transcriptional regulation and posttranslational modifications...
December 2016: Translational Cancer Research
https://www.readbyqxmd.com/read/28794159/p63%C3%AE-protein-upregulates-heat-shock-protein-70-expression-via-e2f1-transcription-factor-1-promoting-wasf3-wave3-mmp9-signaling-and-bladder-cancer-invasion
#2
Honglei Jin, Qipeng Xie, Xirui Guo, Jiheng Xu, Annette Wang, Jingxia Li, Junlan Zhu, Xue-Ru Wu, Haishan Huang, Chuanshu Huang
Bladder cancer (BC) is the sixth most common cancer in the United States and is the number one cause of death among patients with urinary system malignancies. This makes the identification of invasive regulator(s)/effector(s) as the potential therapeutic targets for managing BC a high priority. p63 is a member of the p53 family of tumor suppressor genes/proteins, plays a role in the differentiation of epithelial tissues, and is believed to function as a tumor suppressor. However, whether and how p63 functions in BC cell invasion after tumorigenesis remains unclear...
August 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28794013/control-mechanisms-in-germ-cells-mediated-by-p53-family-proteins
#3
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
#4
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/28778066/inhibition-of-lsd1-epigenetically-attenuates-oral-cancer-growth-and-metastasis
#5
Saqer F Alsaqer, Mustafa M Tashkandi, Vinay K Kartha, Ya-Ting Yang, Yazeed Alkheriji, Andrew Salama, Xaralabos Varelas, Maria Kukuruzinska, Stefano Monti, Manish V Bais
Lysine-specific demethylase 1 (LSD1) is a nuclear histone demethylase and a member of the amine oxidase (AO) family. LSD1 is a flavin-containing AO that specifically catalyzes the demethylation of mono- and di-methylated histone H3 lysine 4 through an FAD-dependent oxidative reaction. LSD1 is inappropriately upregulated in lung, liver, brain and esophageal cancers, where it promotes cancer initiation, progression, and metastasis. However, unlike other lysine-specific demethylases, the role and specific targets of LSD1 in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28767039/fxr1-regulates-transcription-and-is-required-for-tumor-growth-in-tp53-homozygous-deletion-human-cancers
#6
Yichao Fan, Jiao Yue, Mengtao Xiao, Han Han-Zhang, Yao Vickie Wang, Chun Ma, Zhilin Deng, Yingxiang Li, Yanyan Yu, Xinghao Wang, Shen Niu, Youjia Hua, Zhiping Weng, Peter Atadja, En Li, Bin Xiang
Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other responses. Homozygous TP53 deletion occurs in various types of human cancers for which no therapeutic strategies have yet been reported. Based on TCGA database analysis, TP53 homozygous deletion locus mostly exhibits co-deletion of the neighboring gene FXR2, which belongs to the Fragile X gene family. Here, we demonstrate that inhibition of the remaining family member FXR1 selectively blocks cell proliferation in cancer cells containing homozygous deletion of both TP53 and FXR2 in a collateral lethality manner...
August 2, 2017: ELife
https://www.readbyqxmd.com/read/28757908/lysosomes-as-oxidative-targets-for-cancer-therapy
#7
REVIEW
Rebecca F Dielschneider, Elizabeth S Henson, Spencer B Gibson
Lysosomes are membrane-bound vesicles that contain hydrolases for the degradation and recycling of essential nutrients to maintain homeostasis within cells. Cancer cells have increased lysosomal function to proliferate, metabolize, and adapt to stressful environments. This has made cancer cells susceptible to lysosomal membrane permeabilization (LMP). There are many factors that mediate LMP such as Bcl-2 family member, p53; sphingosine; and oxidative stress which are often altered in cancer. Upon lysosomal disruption, reactive oxygen species (ROS) levels increase leading to lipid peroxidation, mitochondrial dysfunction, autophagy, and reactive iron...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28714514/nuclear-expression-of-y-box-binding-1-is-important-for-resistance-to-chemotherapy-including-gemcitabine-in-tp53-mutated-bladder-cancer
#8
Takahisa Yamashita, Morihiro Higashi, Shuji Momose, Makoto Morozumi, Jun-Ichi Tamaru
The development and acquisition of multiple drug resistance in cancer cells remain a major obstacle in the treatment of bladder cancer. Nuclear translocation of Y box binding-1 (YB-1), which is a member of a family of DNA-binding proteins that contain a cold shock domain, plays a significant role in the acquisition of drug resistance by upregulating expression of the multidrug resistance-1 (MDR-1) gene product, p-glycoprotein. The tumor suppressor protein p53 is thought to be essential for nuclear translocation of YB-1...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28714006/aldh1l1-variant-rs2276724-and-mrna-expression-predict-post-operative-clinical-outcomes-and-are-associated-with-tp53-expression-in-hbv-related-hepatocellular-carcinoma
#9
Guangzhi Zhu, Xiwen Liao, Chuangye Han, Xiaoguang Liu, Long Yu, Wei Qin, Sicong Lu, Hao Su, Zhiwei Chen, Zhengtao Liu, Yu Liang, Jianlu Huang, Tingdong Yu, Chengkun Yang, Ketuan Huang, Liming Shang, Xinping Ye, Lequn Li, Xue Qin, Kaiyin Xiao, Minhao Peng, Tao Peng
Aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is downregulated in hepatocellular carcinoma (HCC) tumors, and its decreased expression is associated with the poor prognosis of HCC patients. We, therefore, evaluated the effect of single nucleotide polymorphisms (SNPs) of ALDH1L1, and its mRNA expression on the survival of hepatitis B virus (HBV)‑related HCC patients and the association with tumor protein p53 (TP53) expression. ALDH1L1 SNPs in 415 HBV-related HCC patients were genotyped via direct sequencing...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713991/pien-tze-huang-gan-bao-attenuates-carbon-tetrachloride%C3%A2-induced-hepatocyte-apoptosis-in-rats-associated-with-suppression-of-p53-activation-and-oxidative-stress
#10
Jinyan Zhao, Yuchen Zhang, Yun Wan, Haixia Hu, Zhenfeng Hong
Pien Tze Huang Gan Bao (PZH‑GB), a traditional Chinese medicine, has been used for thousands of years as a protective remedy effective against liver injury induced by excessive alcohol and smoking. The present study aimed to evaluate the protective effects and potential mechanisms of PZH‑GB against carbon tetrachloride (CCl4)‑induced hepatic injury. Rats were pre‑treated with silymarin (50 mg/kg) or different doses of PZH‑GB (150, 300 or 600 mg/kg) orally administered for 7 days. At the end of treatment, the rats were intraperitoneally injected with CCl4, or control rats received a corn oil injection...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28706153/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#11
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
July 6, 2017: Oncotarget
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
#12
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/28693246/genetic-alterations-in-japanese-extrahepatic-biliary-tract-cancer
#13
Rei Noguchi, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Yumi Terakado, Yasunori Ohta, Naohide Yamashita, Osamu Kainuma, Sana Yokoi, Yoshiaki Maru, Hiroki Nagase, Yoichi Furukawa
Biliary tract cancer (BTC) is one of the most devastating types of malignant neoplasms worldwide. However, the mechanisms underlying the development and progression of BTC remain unresolved. BTC includes extrahepatic bile duct carcinoma (EBDC), gallbladder carcinoma (GBC) and ampulla of Vater carcinoma (AVC), named according to the location of the tumor. Although genetic alterations of intrahepatic cholangiocarcinoma have been investigated, those of EBDC, GBC and AVC have not yet been fully understood. The present study analyzed somatic mutations of 50 cancer-associated genes in 27 Japanese BTC cells, including: 11 EBDC, 14 GBC and 2 AVC...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28684422/curcumin-shifts-ras-induced-pro-proliferative-mek-erk-signaling-toward-pro-apoptotic-p38mapk-jnk1-signaling-triggering-p53-activation-and-apoptosis
#14
Shuvomoy Banerjee, Pushpak Bhattacharjee, Juni Chakraborty, Abir K Panda, Arnab Bandyopadhyay, Suman K Banik, Gaurisankar Sa
Oncogenic RAS is primarily associated with potent mitogenic ability, and RAS mutants also have an apoptogenic activity, which is poorly understood. Therefore, exploring the signaling circuit that shifts RAS-signals from pro-proliferative to death pathways may provide some molecular clues to the missing link between the mitogenic and apoptogenic mechanisms. Here, we used a systems biology approach exploiting microarray data and employing a mathematical model to better understand the dual role of oncogenic RAS This approach revealed that a curcumin-based intervention shifts the oncogenic RAS-induced MEK/ERK pro-proliferative pathway toward p38MAPK/JNK1 pro-death signaling...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28673313/mdm2-x-inhibitors-under-clinical-evaluation-perspectives-for-the-management-of-hematological-malignancies-and-pediatric-cancer
#15
REVIEW
Veronica Tisato, Rebecca Voltan, Arianna Gonelli, Paola Secchiero, Giorgio Zauli
The two murine double minute (MDM) family members MDM2 and MDMX are at the center of an intense clinical assessment as molecular target for the management of cancer. Indeed, the two proteins act as regulators of P53, a well-known key controller of the cell cycle regulation and cell proliferation that, when altered, plays a direct role on cancer development and progression. Several evidence demonstrated that functional aberrations of P53 in tumors are in most cases the consequence of alterations on the MDM2 and MDMX regulatory proteins, in particular in patients with hematological malignancies where TP53 shows a relatively low frequency of mutation while MDM2 and MDMX are frequently found amplified/overexpressed...
July 3, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28660664/engaging-ly-6a-sca-1-triggers-lipid-raft-dependent-and-independent-responses-in-cd4-t-cell-lines
#16
Melissa A Lang, Sultan A Jenkins, Phillip Balzano, Adeyinka Owoyele, Akshay Patel, Anil K Bamezai
INTRODUCTION: The lymphocyte antigen 6 (Ly-6) supergene family encodes proteins of 12-14 kda in molecular mass that are either secreted or anchored to the plasma membrane through a glycosyl-phosphatidylinisotol (GPI) lipid anchor at the carboxy-terminus. The lipidated GPI-anchor allows localization of Ly-6 proteins to the 10-100 nm cholesterol-rich nano-domains on the membrane, also known as lipid rafts. Ly-6A/Sca-1, a member of Ly-6 gene family is known to transduce signals despite the absence of transmembrane and cytoplasmic domains...
June 28, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28635633/new-insights-in-thyroid-cancer-and-p53-family-proteins
#17
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/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#18
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28623098/acquired-inhibition-of-microrna-124-protects-against-spinal-cord-ischemia-reperfusion-injury-partially-through-a-mitophagy-dependent-pathway
#19
Kun Liu, Lihui Yan, Xiaojing Jiang, Yang Yu, Hongbo Liu, Tianxiang Gu, Enyi Shi
OBJECTIVE: Mitophagy results in selective clearance of damaged mitochondria. We investigated whether mitophagy was involved in the neuroprotection by inhibiting microRNA (miRNA)-124 on ischemic spinal cords. METHODS: Inhibition of miRNA-124 was conducted by intrathecal injection of lentivirus vectors containing antagomiR-124. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 14 minutes. Hind-limb motor function was assessed with the motor deficit index (MDI)...
May 23, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28618116/differences-in-p53-status-significantly-influence-the-cellular-response-and-cell-survival-to-1-25-dihydroxyvitamin-d3-metformin-cotreatment-in-colorectal-cancer-cells
#20
Mohamed A Abu El Maaty, Wendy Strassburger, Tooba Qaiser, Yasamin Dabiri, Stefan Wölfl
Mutations in the tumor suppressor p53 are highly prevalent in cancers and are known to influence the sensitivity of cells to various chemotherapeutics including the anti-cancer candidates 1,25-dihydrovitamin D3 [1,25D3] and metformin. Previous studies have demonstrated additive/synergistic anti-cancer effects of the 1,25D3-metformin combination in different models, however the influence of p53 status on the efficacy of this regimen has not been investigated. The CRC cell lines HCT116 wild-type (wt), HCT116 p53-/- and HT-29 (mutant; R273H) were employed, covering 3 different p53 variations...
June 15, 2017: Molecular Carcinogenesis
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