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https://www.readbyqxmd.com/read/28439015/mutant-p53-perturbs-dna-replication-checkpoint-control-through-topbp1-and-treslin
#1
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...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415779/relationship-of-p73-gene-polymorphism-and-additional-gene-smoking-and-gene-obesity-interaction-with-non-small-cell-lung-cancer-risk
#2
Qiuge Wu, Yan Shi, Lulu Ge, Dongbo Ma, Hui Zhang, Jing Wang
AIM: The aim of this study was to investigate the impact of G4C14-to-A4T14 polymorphism within P73 gene and additional interactions with current smoking and obesity on non-small cell lung cancer (NSCLC) risk in a Chinese population. RESULTS: Logistic regression analysis showed a significant association between genotypes of the AT allele in G4C14-to-A4T14 and decreased NSCLC risk. NSCLC risk was significantly lower in carriers of the G4C14-to-A4T14- AT allele than those with GC/GC genotype (AT/AT + GC/AT versus GC/GC), adjusted OR (95%CI) = 0...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415683/suppression-of-pkc-causes-oncogenic-stress-for-triggering-apoptosis-in-cancer-cells
#3
Suthakar Ganapathy, Bo Peng, Ling Shen, Tianqi Yu, Jean Lafontant, Ping Li, Rui Xiong, Alexandros Makriyannis, Changyan Chen
Gain of functional mutations in ras occurs in more than 30% of human malignancies and in particular 90% of pancreatic cancer. Mutant ras, via activating multiple effector pathways, not only promote cell growth or survival, but also apoptosis, depending upon cell types or circumstances. In order to further study the mechanisms of apoptosis induced by oncogenic ras, we employed the ras loop mutant genes and demonstrated that Akt functioned downstream of Ras in human pancreatic cancer or HPNE cells ectopically expressing mutated K-ras for the induction of apoptosis after the concurrent suppression of PKC α and β...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409295/metal-chelator-tpen-selectively-induces-apoptosis-in-k562-cells-through-reactive-oxygen-species-signaling-mechanism-implications-for-chronic-myeloid-leukemia
#4
Luisa Rojas-Valencia, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio
Chronic myeloid leukemia (CML) is a hematologic disorder characterized by the constitutive expression of BCR-ABL tyrosine kinase. Although successful implementation of tyrosine kinase inhibitors for the treatment of CML remain a traditional choice for molecularly targeted therapy, some patients present primary or secondary resistance to such therapy. Therefore, alternative therapeutic strategies are required to treat resistant CML cells. Accordingly, new anti-proliferative and/or pro-apoptotic compounds would be needed for clinical treatment...
April 13, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28403886/the-long-non-coding-rna-tp73-as1-modulates-hcc-cell-proliferation-through-mir-200a-dependent-hmgb1-rage-regulation
#5
Shaling Li, Yan Huang, Yun Huang, Yongming Fu, Daolin Tang, Rui Kang, Rongrong Zhou, Xue-Gong Fan
BACKGROUND: P73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation. METHODS: TP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed...
April 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28389140/sex-differences-in-aripiprazole-sensitization-from-adolescence-to-adulthood
#6
Elizabeth Freeman, Joanne Lin, Shinnyi Chow, Collin Davis, Ming Li
The present study investigated the potential sex differences in repeated aripiprazole (ARI) treatment-induced behavioral sensitization from adolescence to adulthood, and to determine whether ARI sensitization can be transferred to olanzapine (OLZ) and/or clozapine (CLZ) using the conditioned avoidance response (CAR) and phencyclidine-induced (PCP) hyperlocomotion tests of antipsychotic activity. Male and female Sprague-Dawley adolescence rats (P46) were first treated with ARI (10mg/kg) for 5 consecutive days (P46-50) and tested for avoidance response and ARI-induced inhibition of PCP-induced hyperlocomotion...
April 4, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28379612/the-long-non-coding-rna-tp73-as1-interacted-with-mir-142-to-modulate-brain-glioma-growth-through-hmgb1-rage-pathway
#7
Rong Zhang, Hekun Jin, Fan Lou
P73 antisense RNA 1T (non-protein coding), also known as TP73-AS1 or PDAM, is a long non-coding RNA which may regulate apoptosis via regulation of p53-dependent anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In the present study, TP73-AS1 was specifically upregulated in brain glioma tissues and cell lines and was associated with poorer prognosis in patients with glioma...
April 5, 2017: Journal of Cellular Biochemistry
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
#8
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
https://www.readbyqxmd.com/read/28278226/correction-phytometabolite-dehydroleucodine-induces-cell-cycle-arrest-apoptosis-and-dna-damage-in-human-astrocytoma-cells-through-p73-p53-regulation
#9
Natalia Bailon-Moscoso, Gabriela González-Arévalo, Gabriela Velásquez-Rojas, Omar Malagon, Giovanni Vidari, Alejandro Zentella-Dehesa, Edward A Ratovitski, Patricia Ostrosky-Wegman
[This corrects the article DOI: 10.1371/journal.pone.0136527.].
2017: PloS One
https://www.readbyqxmd.com/read/28257089/blockade-of-y177-and-nuclear-translocation-of-bcr-abl-inhibits-proliferation-and-promotes-apoptosis-in-chronic-myeloid-leukemia-cells
#10
Qianyin Li, Zhenglan Huang, Miao Gao, Weixi Cao, Qin Xiao, Hongwei Luo, Wenli Feng
The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear...
March 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28239803/nasal-hppsis-administration-enhances-ngf-and-tumor-suppressor-protein-p73-in-human-brain-cancer-tissues-preliminary-data
#11
L Aloe, M L Rocco, E Stigliano, F Angelini, M Iacoangeli, V Frari, F Salvinelli
OBJECTIVE: Nerve Growth Factor (NGF) is a neurotrophic factor known to play a critical role in growth, survival, differentiation and neuroprotection of peripheral sensory and sympathetic neurons, as well as brain neurons. We have recently reported that nasal administration of high-pressure isotonic physiological saline solution (HPpSIS) enhances the level of NGF and the expression of NGF receptors in neurons of the olfactory bulbs and forebrain cholinergic neurons of laboratory animals...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28236663/catalytic-competence-structure-and-stability-of-the-cancer-associated-r139w-variant-of-the-human-nad-p-h-quinone-oxidoreductase-1-nqo1
#12
Wolf-Dieter Lienhart, Emilia Strandback, Venugopal Gudipati, Karin Koch, Alexandra Binter, Michael K Uhl, David M Rantasa, Benjamin Bourgeois, Tobias Madl, Klaus Zangger, Karl Gruber, Peter Macheroux
The human NAD(P)H:quinone oxidoreductase 1 (NQO1; EC1.6.99.2) is an essential enzyme in the antioxidant defence system. Furthermore, NQO1 protects tumour suppressors like p53, p33(ING)(1b) and p73 from proteasomal degradation. The activity of NQO1 is also exploited in chemotherapy for the activation of quinone-based treatments. Various single nucleotide polymorphisms are known, such as NQO1*2 and NQO1*3 yielding protein variants of NQO1 with single amino acid replacements, i.e. P187S and R139W, respectively...
April 2017: FEBS Journal
https://www.readbyqxmd.com/read/28235466/trifluoroethanol-induced-conformational-transition-of-the-c-terminal-sterile-alpha-motif-sam-of-human-p73
#13
José L Neira, Ana Cámara-Artigas
The alpha splice variant of p73 (p73α), a homologue of the tumour suppressor p53, has at its C terminus a sterile alpha motif (SAM); this domain, SAMp73, is involved in lipid binding and it is thought to mediate in protein-protein interactions. As SAMp73 is a 68-residue-long helical bundle, it could be a good model to study the (2,2,2-trifluoroethanol) TFE-induced conformational transitions of α-helical proteins. Furthermore, as SAMp73 binds to lipids through a well-known polypeptide patch, we can test whether TFE is a good mimic of lipids and membranes...
April 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28219820/versatile-carboxyl-terminus-of-capsid-protein-of-porcine-circovirus-type-2-were-recognized-by-monoclonal-antibodies-with-pluripotency-of-binding
#14
Ling-Chu Hung, Ivan-Chen Cheng
We designed the peptide (C3) mimetic carboxyl-terminus (Cterminus) of capsid protein of porcine circovirus type 2b (PCV2b-1A/1B) inducing humoral immunity and generating hybridomas. The positive reactivity of the mAbs to PCV2 capsid protein was demonstrated by Western blot assay. Those mAbs also showed positive signals on PCV2b infected swine lymphocytes by indirect immunofluorescence staining. The mAb 1H3 bound to three minimal linear epitopes (P62, DPPLNP; P67, DPPLNPK; P73, LKDPPLKP), which was located at Cterminus of the capsid protein of PCV2b-1A/1B, PCV2b-1C, and PCV2a-2A respectively...
March 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28212736/tap73-upregulates-il-1%C3%AE-in-cancer-cells-potential-biomarker-in-lung-and-breast-cancer
#15
Polina Vikhreva, Varvara Petrova, Tarik Gokbulut, Ilias Pestlikis, Mara Mancini, Nicola Di Daniele, Richard A Knight, Gerry Melino, Ivano Amelio
p73 is a transcription factor belonging to the p53 tumour suppressor family. p73(-/-) mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β is tightly regulated by large protein complexes, named inflammasomes...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28211873/the-p53-family-members-have-distinct-roles-during-mammalian-embryonic-development
#16
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/28187431/recombinant-adeno-associated-virus-expressing-a-p53-derived-apoptotic-peptide-37aa-inhibits-hcc-cells-growth-in-vitro-and-in-vivo
#17
Hongyong Zhang, Yufeng Wang, Yanxia Bai, Yuan Shao, Jigang Bai, Zhenhua Ma, Qingguang Liu, Shengli Wu
Recent studies have confirmed that a p53-derived apoptotic peptide (37AA) could act as a tumor suppressor inducing apoptosis in multiple tumor cells through derepressing p73. However, the tumor suppressive effects of recombinant adeno-associated virus (rAAV) expressing 37AA on HCC cells are still unknown. In this study, we successfully constructed a recombinant rAAV expressing 37AA. In vitro and in vivo assays showed that transfection of NT4-37AA/rAAV in HCC cells strongly suppressed cell proliferation, induced apoptosis, and up-regulated the cellular expression of p73...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28134496/p73-g4c14-to-a4t14-polymorphism-is-associated-with-survival-in-advanced-non-small-cell-lung-cancer-patients
#18
Lei Ge, Yang Yang, Yifeng Sun, Wen Xu, Daru Lu, Bo Su
BACKGROUND: p73, a structural and functional homolog of p53, plays an important role in modulating cell cycle arrest. This study investigated the association between p73 G4C14-to-A4T14 polymorphism and survival outcomes in a Chinese population of advanced non-small cell lung cancer (NSCLC) patients treated with platinum agents. METHODS: The p73 G4C14-to-A4T14 polymorphism was genotyped using DNA from blood samples of advanced NSCLC patients (642 in the discovery set and 330 in the replication set)...
March 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28128397/meta-analysis-of-tp73-polymorphism-and-cervical-cancer
#19
H Feng, L Sui, M Du, Q Wang
The aim of this study was to investigate the tumor protein p73 (TP73) G4C14-A4T14 polymorphism and to perform a meta-analysis to assess TP73 expression in cervical cancer and precancerous tissue. Articles containing data regarding TP73 status in cervical cancer patients and healthy controls were retrieved from PubMed, EMBASE, Cochrane, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases. Then, the quality of the studies was evaluated according to inclusion and exclusion criteria...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28122957/phosphoglycerate-mutase-1-regulates-dntp-pool-and-promotes-homologous-recombination-repair-in-cancer-cells
#20
Jia Qu, Wenyi Sun, Jie Zhong, Hao Lv, Mingrui Zhu, Jun Xu, Nan Jin, Zuoquan Xie, Minjia Tan, Shu-Hai Lin, Meiyu Geng, Jian Ding, Min Huang
Glycolytic enzymes are known to play pivotal roles in cancer cell survival, yet their molecular mechanisms remain poorly understood. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that coordinates glycolysis, pentose phosphate pathway, and serine biosynthesis in cancer cells. Herein, we report that PGAM1 is required for homologous recombination (HR) repair of DNA double-strand breaks (DSBs) caused by DNA-damaging agents. Mechanistically, PGAM1 facilitates DSB end resection by regulating the stability of CTBP-interacting protein (CtIP)...
February 2017: Journal of Cell Biology
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