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promyelocytic leukemia protein

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https://www.readbyqxmd.com/read/27913186/protein-kinase-a-activation-by-retinoic-acid-in-the-nuclei-of-hl60-cells
#1
Asako Sakai, Masahiko Imai, Katsuhiko Takahashi, Shinya Hasegawa, Masahiro Yamasaki, Toshihiro Ohba, Noriko Takahashi
BACKGROUND: Activation of protein kinase A (PKA) occurs during retinoic acid (RA)-induced granulocytic differentiation of human promyelocytic leukemia HL60 cells. It is known that the RIIα regulatory subunit of PKA, is modified by RA (retinoylated) in the early stages of differentiation. We have investigated the effects of RA on PKA during cell differentiation in order to understand the potential significance of this process in the retinoylation of RIIα subunits. METHODS: Immunoblotting, immunoprecipitation, confocal microscopy, PCR, and PKA activity assays were employed for characterizing the effects of RA on PKA...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27895727/deficiency-of-sumo-specific-protease-1-induces-arsenic-trioxide-mediated-apoptosis-by-regulating-xbp1-activity-in-human-acute-promyelocytic-leukemia
#2
Fei-Fei Wang, Ming-Zhu Liu, Yi Sui, Qing Cao, Bo Yan, Mei-Ling Jin, Xi Mo
Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER) stress, resulting in the apoptosis of NB4 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27888400/repression-of-cdkn2c-caused-by-pml-rar%C3%AE-binding-promotes-the-proliferation-and-differentiation-block-in-acute-promyelocytic-leukemia
#3
Xiaoling Wang, Yun Tan, Yizhen Li, Jingming Li, Wen Jin, Kankan Wang
Inappropriate cell proliferation during oncogenesis is often accompanied by inactivation of components involved in the cell cycle machinery. Here, we report that cyclin-dependent kinase inhibitor 2C (CDKN2C) as a member of the cyclin-dependent kinase inhibitors is a target of the PML/RARα oncofusion protein in leukemogenesis of acute promyelocytic leukemia (APL).We found that CDKN2C was markedly downregulated in APL blasts compared with normal promyelocytes. Chromatin immunoprecipitation combined with quantitative polymerase chain reaction demonstrated that PML/RARα directly bound to the CDKN2C promoter in the APL patient-derived cell line NB4...
November 23, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27833854/human-promyelocytic-leukemia-protein-is-targeted-to-distinct-subnuclear-domains-in-plant-nuclei-and-colocalizes-with-nucleolar-constituents-in-a-sumo-dependent-manner
#4
Christian E Lamm, Myriam Scherer, Nina Reuter, Bushra Amin, Thomas Stamminger, Uwe Sonnewald
Eukaryotic nuclei are subdivided into subnuclear structures. Among the most prominent of these structures are the nucleolus and the PML nuclear bodies (PML-NBs). PML-NBs are spherical multiprotein aggregates of varying size localized in the interchromosomal area. PML-NB formation is dependent on the presence of the promyelocytic leukemia protein (PML) as well as on post-translational modification of core components by covalent attachment of the small ubiquitin-like modifier (SUMO). So far, PML-NBs as well as PML have been described in mammalian cells only, whereas no orthologs are known in the plant kingdom...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27833022/hdac9-regulates-the-alternative-lengthening-of-telomere-alt-pathway-via-the-formation-of-alt-associated-pml-bodies
#5
Mohd Raeed Jamiruddin, Taku Kaitsuka, Farzana Hakim, Atsushi Fujimura, Fan-Yan Wei, Hisato Saitoh, Kazuhito Tomizawa
Cancer cells overcome cellular senescence by activating the telomere maintenance mechanism, which can be either through telomerase or the alternative lengthening of telomeres (ALT). Being exclusive to cancer cells, targeting ALT is a more promising route for the development of drugs against cancer. The histone deacetylase (HDAC) family plays significant roles in various cellular processes. In addition to the regulation of gene expression, HDACs are also known to directly interact with many proteins. We focused on this family, and found that HDAC9 was up-regulated in ALT-positive cells...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27785739/a-selenium-modified-ginseng-polysaccharide-promotes-the-apoptosis-in-human-promyelocytic-leukemia-hl-60-cells-via-a-mitochondrial-mediated-pathway
#6
Kainan Liao, Zedong Bian, Dongke Xie, Qiang Peng
A ginseng polysaccharide was extracted, purified, and modified by nitric acid-selenious acid (HNO3-H2SeO3) method to yield one selenylation-modified polysaccharide (sGP). We reported for the first time the anticancer potential of sGP on the human promyelocytic leukemia HL-60 cell line and evaluated its relevant underlying mechanism. Our results showed that sGP markedly inhibited the growth of HL-60 cells via induction of apoptosis. The event of apoptosis was accompanied by the formation of apoptotic bodies; the release of cytochrome c; loss of mitochondrial membrane potential; and activation of caspase-9, caspase-3, and cleavage of poly ADP ribose polymerase (PARP) in HL-60 cells...
October 26, 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/27782081/the-role-of-nuclear-antiviral-factors-against-invading-dna-viruses-the-immediate-fate-of-incoming-viral-genomes
#7
REVIEW
Tetsuro Komatsu, Kyosuke Nagata, Harald Wodrich
In recent years, it has been suggested that host cells exert intrinsic mechanisms to control nuclear replicating DNA viruses. This cellular response involves nuclear antiviral factors targeting incoming viral genomes. Herpes simplex virus-1 (HSV-1) is the best-studied model in this context, and it was shown that upon nuclear entry HSV-1 genomes are immediately targeted by components of promyelocytic leukemia nuclear bodies (PML-NBs) and the nuclear DNA sensor IFI16 (interferon gamma inducible protein 16). Based on HSV-1 studies, together with limited examples in other viral systems, these phenomena are widely believed to be a common cellular response to incoming viral genomes, although formal evidence for each virus is lacking...
October 22, 2016: Viruses
https://www.readbyqxmd.com/read/27770503/survivin-isoform-expression-in-arsenic-trioxide-treated-acute-promyelocytic-leukemia-cell-line-and-patients-the-odd-expression-pattern-of-survivin-2%C3%AE
#8
Majid Zaki Dizaji, Seyed H Ghaffari, Elham Hosseini, Nasrin Alizadeh, Shahrbano Rostami, Majid Momeny, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
AIM: Survivin, an inhibitor of apoptosis protein, is overexpressed in most cancers and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. Several survivin splice variants have been described, and none of their expressions have been defined in acute promyelocytic leukemia (APL). METHODS: Expression of the survivin gene isoforms (survivin, -2α, -2B, -ΔΕx3 and -3B) were analyzed in 50 peripheral blood and 19 bone marrow samples that were collected at different phases of the disease (diagnostic, remission and relapse) in APL patients treated with arsenic trioxide (ATO) as a front-line therapy...
October 22, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27761836/analyzing-the-impact-of-pan-and-class-specific-hdaci-on-differentiation-associated-factors
#9
Katrin Noack, Oliver H Krämer
The differentiation of hematopoietic stem cells into mature blood cells is a highly ordered process and dysregulation of this process can lead to leukemogenesis. Agents that are used to cure acute promyelocytic leukemia (APL) can induce differentiation and/or apoptosis. Here, we describe how effects of all-trans retinoic acid (ATRA) and histone deacetylase inhibitors (HDACi) on APL cell differentiation can be evaluated by immunoblotting and by flow cytometry. We show how the levels of differentiation-associated transcription factors of the CCAAT enhancer binding protein (C/EBP) family can be determined by Western blot and we explain how the cell surface expression of the leukocyte surface antigen CD11b can be measured by flow cytometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27758112/pml-a-protein-at-the-cross-road-of-oxidative-stress-and-metabolism
#10
Sarah Tessier, Natalia Martin-Martin, Hugues de Thé, Arkaitz Carracedo, Valerie Lallemand-Breitenbach
SIGNIFICANCE: Cellular metabolic activity impacts on the production of reactive oxygen species (ROS), both positively through mitochondrial oxidative processes and negatively by promoting the production of reducing agents (including NADPH and reduced glutathione). A defined metabolic state in cancer cells is critical for cell growth and long-term self-renewal, and such state is intrinsically associated to redox balance. Promyelocytic leukemia protein (PML) regulates several biological processes, at least in part through its ability to control the assembly of PML Nuclear Bodies (PML NBs)...
October 19, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27748945/survivint34a-increases-the-therapeutic-efficacy-of-arsenic-trioxide-in-mouse-hepatocellular-carcinoma-models
#11
Anliang Huang, Dan Yue, Danying Liao, Liuliu Cheng, Jinhu Ma, Yuquan Wei, Aiping Tong, Ping Cheng
Arsenic trioxide (ATO) has demonstrated clinical efficacy in acute promyelocytic leukemia (APL) and in vitro activity in various solid tumors. As2O3 as single agent exhibits poor efficacy for treatment of hepatocellular carcinoma (HCC) in phase II trial, suggesting that new modalities of treatment with enhanced therapeutic effect and alleviated toxicity are needed for application of As2O3 on patients with HCC. Survivin is the strongest inhibitor of apoptosis protein over-expressed in tumors, which has been proposed as an attractive target for new anticancer interventions...
October 11, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27732960/selenite-promotes-all-trans-retinoic-acid-induced-maturation-of-acute-promyelocytic-leukemia-cells
#12
Sougat Misra, Arun Kumar Selvam, Marita Wallenberg, Aditya Ambati, András Matolcsy, Isabelle Magalhaes, Gilbert Lauter, Mikael Björnstedt
Selective targeting of the PML/RARα oncoprotein demonstrates a successful molecular targeted therapy in acute promyelocytic leukemia (APL) with a typical t(15:17) chromosomal translocation. The zinc-thiolate coordination is critical for structural stability of zinc finger proteins, including the PML moiety of PML/RARα. Based on the known interaction of redox-active selenium compounds with thiolate ligands of zinc, we herein have investigated the abrogatory effects of selenite alone or in combination with all-trans retinoic acid on PML/RARα and the possible effects on differentiation in these cells...
October 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27727328/targeting-of-the-plzf-gene-in-the-rat-by-transcription-activator-like-effector-nuclease-results-in-caudal-regression-syndrome-in-spontaneously-hypertensive-rats
#13
František Liška, Renata Peterková, Miroslav Peterka, Vladimír Landa, Václav Zídek, Petr Mlejnek, Jan Šilhavý, Miroslava Šimáková, Vladimír Křen, Colby G Starker, Daniel F Voytas, Zsuzsanna Izsvák, Michal Pravenec
Recently, it has been found that spontaneous mutation Lx (polydactyly-luxate syndrome) in the rat is determined by deletion of a conserved intronic sequence of the Plzf (Promyelocytic leukemia zinc finger protein) gene. In addition, Plzf is a prominent candidate gene for quantitative trait loci (QTLs) associated with cardiac hypertrophy and fibrosis in the spontaneously hypertensive rat (SHR). In the current study, we tested the effects of Plzf gene targeting in the SHR using TALENs (transcription activator-like effector nucleases)...
2016: PloS One
https://www.readbyqxmd.com/read/27720952/retinoylation-covalent-modification-by-retinoic-acid-of-rho-gdi%C3%AE-in-the-human-myeloid-leukemia-cell-line-hl60-and-its-functional-significance
#14
Noriko Takahashi, Toshihiro Ohba, Masahiko Imai, Shinya Hasegawa, Katsuhiko Takahashi, Masahiro Yamasaki, Yuri Kameoka
Retinoic acid (RA) has a variety of biological effects in mammalian cells and tissues. It is well known that RA induces differentiation of human acute promyelocytic leukemia (APL) HL60 cells, fresh human APL cells, and clinical remission in patients with APL. Retinoylation (acylation of proteins by RA) is a possible pathway for RA action. However, an understanding of the role that retinoylation plays in the actions of RA is lacking. In the current study, several retinoylated proteins were detected in RA-treated HL60 fractions following Mono Q anion exchange chromatography and analysis using two-dimensional polyacrylamide gel electrophoresis...
October 6, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27665842/staurosporine-enhances-atra-induced-granulocytic-differentiation-in-human-leukemia-u937-cells-via-the-mek-erk-signaling-pathway
#15
Lei Shi, Xiang-Qin Weng, Yan Sheng, Jing Wu, Ming Ding, Xun Cai
Although all-trans retinoic acid (ATRA) is regarded as a prominent example of differentiation therapy, it is not effective for the treatment of other subtypes of acute myeloid leukemia (AML) beyond acute promyelocytic leukemia (APL). Therefore, new strategies need to be explored to extend the efficacy of ATRA-based therapy to non-APL AML patients. In the present study, staurosporine, a protein kinase C (PKC) pan-inhibitor, exhibited synergism with ATRA to promote granulocytic differentiation in poorly ATRA-sensitive U937 cells but not in ATRA unresponsive K562 and Kasumi cells...
September 23, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27641331/restoration-of-tumor-suppression-in-prostate-cancer-by-targeting-the-e3-ligase-e6ap
#16
P J Paul, D Raghu, A-L Chan, T Gulati, L Lambeth, E Takano, M J Herold, J Hagekyriakou, R L Vessella, C Fedele, M Shackleton, E D Williams, S Fox, S Williams, S Haupt, C Gamell, Y Haupt
Restoration of tumor suppression is an attractive onco-therapeutic approach. It is particularly relevant when a tumor suppressor is excessively degraded by an overactive oncogenic E3 ligase. We previously discovered that the E6-associated protein (E6AP; as classified in the human papilloma virus context) is an E3 ligase that has an important role in the cellular stress response, and it directly targets the tumor-suppressor promyelocytic leukemia protein (PML) for proteasomal degradation. In this study, we have examined the role of the E6AP-PML axis in prostate cancer (PC)...
December 1, 2016: Oncogene
https://www.readbyqxmd.com/read/27618691/latency-entry-of-herpes-simplex-virus-1-is-determined-by-the-interaction-of-its-genome-with-the-nuclear-environment
#17
Mohamed Ali Maroui, Aleth Callé, Camille Cohen, Nathalie Streichenberger, Pascale Texier, Julie Takissian, Antoine Rousseau, Nolwenn Poccardi, Jérémy Welsch, Armelle Corpet, Laurent Schaeffer, Marc Labetoulle, Patrick Lomonte
Herpes simplex virus 1 (HSV-1) establishes latency in trigeminal ganglia (TG) sensory neurons of infected individuals. The commitment of infected neurons toward the viral lytic or latent transcriptional program is likely to depend on both viral and cellular factors, and to differ among individual neurons. In this study, we used a mouse model of HSV-1 infection to investigate the relationship between viral genomes and the nuclear environment in terms of the establishment of latency. During acute infection, viral genomes show two major patterns: replication compartments or multiple spots distributed in the nucleoplasm (namely "multiple-acute")...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27613090/identification-of-mir-125b-targets-involved-in-acute-promyelocytic-leukemia-cell-proliferation
#18
Yikai Zhang, Chengwu Zeng, Shuai Lu, Tianyu Qin, Lijian Yang, Shaohua Chen, Jie Chen, Yangqiu Li
Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27610044/selected-polyphenols-potentiate-the-apoptotic-efficacy-of-glycolytic-inhibitors-in-human-acute-myeloid-leukemia-cell-lines-regulation-by-protein-kinase-activities
#19
Elena de Blas, María Cristina Estañ, María Del Carmen Gómez de Frutos, Javier Ramos, María Del Carmen Boyano-Adánez, Patricio Aller
BACKGROUND: The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) is a safe, potentially useful anti-tumour drug, but its efficacy is normally low when used alone. Recent studies indicated that 2-DG stimulates the PI3K/Akt and MEK/ERK defensive pathways, which limits the apoptotic efficacy in tumour cell lines. We hypothesized that co-treatment with selected polyphenols could improve 2-DG-provoked apoptosis by preventing defensive kinase activation. METHODS: Cell proliferation was measured by cell counting or the MTT assay...
2016: Cancer Cell International
https://www.readbyqxmd.com/read/27605212/activation-of-g0s2-is-coordinated-by-recruitment-of-pml-rar%C3%AE-and-c-ebp%C3%AE%C2%B5-to-its-promoter-during-atra-induced-apl-differentiation
#20
Fang Zhang, Yong Lan Zhu, Wang Long Deng, Jiang Zhu, Ji Zhang
All-trans retinoic acid (ATRA) binds the promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein and is an effective oncogene-targeted therapy for acute promyelocytic leukemia (APL). However, the molecular basis of PML/RARα-mediated transcriptional control during ATRA-induced differentiation is unclear. Previous studies have shown that the PML/RARα fusion protein behaves as a type II nuclear receptor, binding to DNA regardless of ligand status. Here, we performed a series of chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) experiments, demonstrating that there is an additional mode of action of PML/RARα, wherein PML/RARα does not bind DNA in the absence of ATRA but binds DNA and activates adjacent genes in the presence of ATRA...
September 7, 2016: Journal of Leukocyte Biology
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