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https://www.readbyqxmd.com/read/29147811/c-terminal-region-of-human-p53-attenuates-buffalo-p53%C3%A2-n-terminal-specific-transactivation-of-p21-promoter-by-modulating-tetramerization-of-the-protein
#1
Minu Singh, Tapas Mukhopadhyay
Here, we have studied in p53 null H1299 lung carcinoma cells, the dominant-negative effect of human p53 (h-p53) on buffalo p53 (b-p53) induced nuclear transactivation-dependent function. Recently, we have isolated and cloned the full-length cDNA of buffalo p53. Buffalo and human p53 proteins exhibit a high degree of structural and functional similarities. In transiently transfected H1299 cell line b-p53 appeared to be more sensitive to Mdm2-mediated degradation as compared to h-p53, although its ability to transactivate p21 promoter was stronger than that of the human counterpart...
November 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29145196/aqp2-abundance-is-regulated-by-the-e3-ligase-chip-via-hsp70
#2
Mariangela Centrone, Marianna Ranieri, Annarita Di Mise, Sante Princiero Berlingerio, Annamaria Russo, Peter M T Deen, Olivier Staub, Giovanna Valenti, Grazia Tamma
BACKGROUND/AIMS: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. METHODS: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting...
November 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29143558/perturbation-of-rna-polymerase-i-transcription-machinery-by-ablation-of-heatr1-triggers-the-rpl5-rpl11-mdm2-p53-ribosome-biogenesis-stress-checkpoint-pathway-in-human-cells
#3
Zsofia Turi, Marketa Senkyrikova, Martin Mistrik, Jiri Bartek, Pavel Moudry
Ribosome biogenesis is an energy consuming process which takes place mainly in the nucleolus. By producing ribosomes to fuel protein synthesis, it is tightly connected with cell growth and cell cycle control. Perturbation of ribosome biogenesis leads to the activation of p53 tumor suppressor protein promoting processes like cell cycle arrest, apoptosis or senescence. This ribosome biogenesis stress pathway activates p53 through sequestration of MDM2 by a subset of ribosomal proteins (RPs), thereby stabilizing p53...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29142290/characterizing-the-conformational-landscape-of-mdm2-binding-p53-peptides-using-molecular-dynamics-simulations
#4
Shilpa Yadahalli, Jianguo Li, David P Lane, Shachi Gosavi, Chandra S Verma
The conformational landscapes of p53 peptide variants and phage derived peptide (12/1) variants, all known to bind to MDM2, are studied using hamiltonian replica exchange molecular dynamics simulations. Complementing earlier observations, the current study suggests that the p53 peptides largely follow the 'conformational selection' paradigm in their recognition of and complexation by MDM2 while the 12/1 peptides likely undergo some element of conformational selection but are mostly driven by 'binding induced folding'...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141234/elevated-p53-activities-restrict-differentiation-potential-of-microrna-deficient-pluripotent-stem-cells
#5
Zhong Liu, Cheng Zhang, Maria Skamagki, Alireza Khodadadi-Jamayran, Wei Zhang, Dexin Kong, Chia-Wei Chang, Jingyang Feng, Xiaosi Han, Tim M Townes, Hu Li, Kitai Kim, Rui Zhao
Pluripotent stem cells (PSCs) deficient for microRNAs (miRNAs), such as Dgcr8(-/-) or Dicer(-/-) embryonic stem cells (ESCs), contain no mature miRNA and cannot differentiate into somatic cells. How miRNA deficiency causes differentiation defects remains poorly understood. Here, we report that miR-302 is sufficient to enable neural differentiation of differentiation-incompetent Dgcr8(-/-) ESCs. Our data showed that miR-302 directly suppresses the tumor suppressor p53, which is modestly upregulated in Dgcr8(-/-) ESCs and serves as a barrier restricting neural differentiation...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29137250/molecular-chaperones-in-the-acquisition-of-cancer-cell-chemoresistance-with-mutated-tp53-and-mdm2-up-regulation
#6
Zuzanna Tracz-Gaszewska, Marta Klimczak, Przemyslaw Biecek, Marcin Herok, Marcin Kosinski, Maciej B Olszewski, Patrycja Czerwińska, Milena Wiech, Maciej Wiznerowicz, Alicja Zylicz, Maciej Zylicz, Bartosz Wawrzynow
Utilizing the TCGA PANCAN12 dataset we discovered that cancer patients with mutations in TP53 tumor suppressor and overexpression of MDM2 oncogene exhibited decreased survival post treatment. Interestingly, in the case of breast cancer patients, this phenomenon correlated with high expression level of several molecular chaperones belonging to the HSPA, DNAJB and HSPC families. To verify the hypothesis that such a genetic background may promote chaperone-mediated chemoresistance, we employed breast and lung cancer cell lines that constitutively overexpressed heat shock proteins and have shown that HSPA1A/HSP70 and DNAJB1/HSP40 facilitated the binding of mutated p53 to the TAp73α protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132330/the-association-of-polymorphic-markers-arg399gln-of-xrcc1-gene-arg72pro-of-tp53-gene-and-t309g-of-mdm2-gene-with-breast-cancer-in-kyrgyz-females
#7
Jainagul Isakova, Elnura Talaibekova, Nazira Aldasheva, Denis Vinnikov, Almaz Aldashev
BACKGROUND: The association of genes XRCC1, TP53 and MDM2 with breast cancer (BC) has never been tested in Kyrgyz population. We, therefore, aimed to identify an association of alleles and genotypes of polymorphic markers Arg399Gln of gene XRCC1, Arg72Pro of gene TP53, and T309G of gene MDM2 with the risk of BC in Kyrgyz women. METHODS: This was a case-control study of 219 women of Kyrgyz origin with morphologically verified BC (N = 117) and 102 controls, age-matched with BC cases...
November 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29129511/dmxaa-pyranoxanthone-hybrids-enhance-inhibition-activities-against-human-cancer-cells-with-multi-target-functions
#8
Jie Liu, Fan Zhou, Lei Zhang, Huailing Wang, Jianrun Zhang, Cao Zhang, Zhenlei Jiang, Yanbing Li, Zhijun Liu, Heru Chen
Four 5,6-dimethylxanthone-4-acetic acid (D) and pyranoxanthone (P) hybrids (D-P-n) were design-synthesized based on multi-target-addressed strategy. D-P-4 was confirmed as the most active agent against HepG-2 cell line growth with an IC50 of 0.216 ± 0.031 μM. Apoptosis analysis indicated different contributions of early/late apoptosis/necrosis to cell death for both monomers, the combination (D + P in 1:1 mol ratio) and D-P-4. They all arrested more cells on S phase. Western Blot implied that D-P-4 regulated p53/MDM2 to a better healthy state...
October 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29128960/a-proteomics-analysis-reveals-9-up-regulated-proteins-associated-with-altered-cell-signaling-in-colon-cancer-patients
#9
Oleg I Kit, Dmitry I Vodolazhsky, Denis S Kutilin, Yaroslav S Enin, Yury A Gevorkyan, Peter V Zolotukhin, Yanis Boumber, Leonid V Kharin, Svetlana B Panina
Colorectal cancer is the second most common cancer in women and third most common cancer in men. Cell signaling alterations in colon cancer, especially in aggressive metastatic tumors, require further investigations. The present study aims to compare the expression pattern of proteins associated with cell signaling in paired tumor and non-tumor samples of patients with colon cancer, as well as to define the cluster of proteins to differentiate patients with non-metastatic (Dukes' grade B) and metastatic (Dukes' grade C&D) colon cancer...
November 11, 2017: Protein Journal
https://www.readbyqxmd.com/read/29127917/a-giant-mediastinal-liposarcoma-weighing-3500g-resected-with-clam-shell-approach-a-case-report-with-review-of-literature
#10
Yasoo Sugiura, Toshinori Hashizume, Hiroyuki Fujimoto, Etsuo Nemoto
INTRODUCTION: Liposarcoma is rare in the mediastinum and is less than 1% of all mediastinal tumors. In the present report, we demonstrated our case and summarized the principal treatment of the mediastinal liposarcoma with literature review. PRESENTATION OF CASE: A 50-year-old man presented at our hospital with complain of dyspnea. Chest radiography showed remarkable cardiomegaly. Computed tomography revealed an anterior mediastinal tumor from the level of the cephalic vein to the diaphragm of bilateral thoracic cavity with fat component...
November 7, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29125602/mechanisms-of-transcriptional-regulation-by-p53
#11
REVIEW
Kelly D Sullivan, Matthew D Galbraith, Zdenek Andrysik, Joaquin M Espinosa
p53 is a transcription factor that suppresses tumor growth through regulation of dozens of target genes with diverse biological functions. The activity of this master transcription factor is inactivated in nearly all tumors, either by mutations in the TP53 locus or by oncogenic events that decrease the activity of the wild-type protein, such as overexpression of the p53 repressor MDM2. However, despite decades of intensive research, our collective understanding of the p53 signaling cascade remains incomplete...
November 10, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29123414/low-grade-central-osteosarcoma-in-proximal-humerus-a-rare-entity
#12
Fan Tang, Li Min, Yong Zhou, Yi Luo, Chongqi Tu
Low-grade central osteosarcoma is a rare subtype of tumor with low-grade malignancy. Currently, wide resection with negative resection margin is the standard treatment for this disease. The role of neoadjuvant chemotherapy in low-grade central osteosarcoma was controversial and was mostly considered for tumors containing high-grade focal areas. Local tumor recurrences often exhibited a tumor with higher histologic grade or differentiation with the potential for metastases. In low-grade central osteosarcoma, timely wide resection after definite diagnosis can result in 5-year survival for almost 90%...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29123181/carnosol-controls-the-human-glioblastoma-stemness-features-through-the-epithelial-mesenchymal-transition-modulation-and-the-induction-of-cancer-stem-cell-apoptosis
#13
Chiara Giacomelli, Simona Daniele, Letizia Natali, Caterina Iofrida, Guido Flamini, Alessandra Braca, M Letizia Trincavelli, Claudia Martini
A high cell proliferation rate, invasiveness and resistance to chemotherapy are the main features of glioblastoma (GBM). GBM aggressiveness has been widely associated both with a minor population of cells presenting stem-like properties (cancer stem-like cells, CSCs) and with the ability of tumor cells to acquire a mesenchymal phenotype (epithelial-mesenchymal transition, EMT). Carnosol (CAR), a natural inhibitor of MDM2/p53 complex, has been attracted attention for its anti-cancer effects on several tumor types, including GBM...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29123033/inactivation-of-the-mdm2-ring-domain-enhances-p53-transcriptional-activity-in-mice
#14
Hui Tian, Nicole R Tackmann, Aiwen Jin, Junnian Zheng, Yanping Zhang
The MDM2 RING domain harbors E3 ubiquitin ligase activity critical for regulating the degradation of tumor suppressor p53, which controls many cellular pathways. The MDM2 RING domain also is required for an interaction with MDMX. Mice containing a substitution in the MDM2 RING domain, MDM2C462A, disrupting MDM2 E3 function and the MDMX interaction, die during early embryogenesis that can be rescued by p53 deletion. To investigate whether MDM2C462A, which retains p53 binding, has p53-suppressing activity, we generated Mdm2C462A/C462A;p53ER/- mice, in which we replaced the endogenous p53 alleles with an inducible p53ER/- allele, and compared survival with that of similarly generated Mdm2-/-;p53ER/- mice...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29122980/correction-hiv-1-tat-potently-stabilises-mdm2-and-enhances-viral-replication
#15
Rameez Raja, Larance Ronsard, Sneh Lata, Shubhendu Trivedi, Akhil C Banerjea
No abstract text is available yet for this article.
November 9, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29121928/a-yeast-two-hybrid-system-for-the-screening-and-characterization-of-small-molecule-inhibitors-of-protein-protein-interactions-identifies-a-novel-putative-mdm2-binding-site-in-p53
#16
Jin Huei Wong, Mohammad Alfatah, Mei Fang Sin, Hong May Sim, Chandra S Verma, David P Lane, Prakash Arumugam
BACKGROUND: Protein-protein interactions (PPIs) are fundamental to the growth and survival of cells and serve as excellent targets to develop inhibitors of biological processes such as host-pathogen interactions and cancer cell proliferation. However, isolation of PPI inhibitors is extremely challenging. While several in vitro assays to screen for PPI inhibitors are available, they are often expensive, cumbersome, and require large amounts of purified protein. In contrast, limited in vivo assays are available to screen for small-molecule inhibitors of PPI...
November 9, 2017: BMC Biology
https://www.readbyqxmd.com/read/29118980/sirt1-dependent-modulation-of-methylation-and-acetylation-of-histone-h3-on-lysine-9-h3k9-in-the-zygotic-pronuclei-improves-porcine-embryo-development
#17
Katerina Adamkova, Young-Joo Yi, Jaroslav Petr, Tereza Zalmanova, Kristyna Hoskova, Pavla Jelinkova, Jiri Moravec, Milena Kralickova, Miriam Sutovsky, Peter Sutovsky, Jan Nevoral
Background: The histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD(+)-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29116067/-apoptosis-as-the-basic-mechanism-of-cytotoxic-action-of-ursolic-and-pomolic-acids-in-glioma-cells
#18
T S Frolova, A V Lipeeva, D S Baev, Y A Tsepilov, O I Sinitsyna
Pentacyclic triterpene acids are of great interest as compounds that exhibit selective cytotoxicity against malignant tumor cells. If earlier studies were carried out mainly in cancer cells of epithelial origin, in the present work the cytotoxic effect of ursolic and pomolic acids on the primary and permanent glioma cell lines was analyzed. Both compounds are toxic to oncotransformed cells and induce apoptosis in U-87 MG line. Using molecular docking, it has been shown that Akt1 and MDM2 may be potential targets of the studied triterpene acids...
September 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29115437/simvastatin-enhances-the-radiosensitivity-of-p53%C3%A2-deficient-cells-via-inhibition-of-mouse-double-minute-2-homolog
#19
Ji Young Lee, Mi-Sook Kim, Jae Eun Ju, Mi So Lee, Namhyun Chung, Youn Kyoung Jeong
Simvastatin exhibits anticancer activities, but its molecular mechanisms and radiosensitizing effects relative to p53 status remain unclear. In this study, we investigated whether the combination of simvastatin and ionizing radiation (IR) would enhance the antitumor effects of IR alone in HCT116 p53+/+ and p53‑/- colon cancer cells. Using colony formation assays and a xenograft mouse model, we found that simvastatin potently stimulated radiosensitization of HCT116 p53‑/- cells and xenograft tumors. The combination of simvastatin with IR decreased G2/M arrest and delayed the repair of IR-induced DNA damage; however, no differences between the HCT116 p53+/+ and p53‑/- cells were evident...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29115375/persistent-stat5-mediated-ros-production-and-involvement-of-aberrant-p53-apoptotic-signaling-in-the-resistance-of-chronic-myeloid-leukemia-to-imatinib
#20
Yanhong Cheng, Yingchan Hao, Aimei Zhang, Chaojie Hu, Xiaoxiao Jiang, Quan Wu, Xiucai Xu
The persistent activation of signal transducer and activator of transcription 5 (STAT5) may principally be attributed to breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1), and have multi-faceted effects in the development of chronic myeloid leukemia (CML). The p53 protein network regulates important mechanisms in DNA damage repair, cell cycle regulation/checkpoints, and cell senescence and apoptosis, as demonstrated by its ability to positively regulate the expression of various pro-apoptotic genes, including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax)...
October 20, 2017: International Journal of Molecular Medicine
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