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https://www.readbyqxmd.com/read/28630090/t-cell-transcriptomes-from-paroxysmal-nocturnal-hemoglobinuria-patients-reveal-novel-signaling-pathways
#1
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Danielle M Townsley, Xingmin Feng, Neal S Young
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#2
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28618963/noxin-promotes-proliferation-of-breast-cancer-cells-via-p38-atf2-signaling-pathway
#3
Xiupeng Zhang, Yong Zhang, Chuifeng Fan, Liang Wang, Yang Liu, Ailin Li, Guiyang Jiang, Haijing Zhou, Lin Cai, Yuan Miao
Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage ( p = 0...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#4
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, Chi Hu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28509555/differential-phosphoproteomic-analysis-of-recombinant-chinese-hamster-ovary-cells-following-temperature-shift
#5
Michael Henry, Martin Power, Prashant Kaushik, Orla Coleman, Martin Clynes, Paula Meleady
Phosphorylation is one of the most important post-translational modifications, playing a crucial role in regulating many cellular processes, including transcription, cytoskeletal rearrangement, cell proliferation, differentiation, apoptosis, and signal transduction. However, to date, little work has been carried out on the phosphoproteome in CHO cells. In this study we have carried out a large scale differential phosphoproteomic analysis of recombinant CHO cells following a reduction of culture temperature (temperature shift)...
June 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28479419/novel-tumor-suppressor-function-of-klf4-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#6
REVIEW
Ye Shen, Taylor J Chen, H Daniel Lacorazza
Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy in pediatric patients. Despite advances in the treatment of this disease, many children with T-cell ALL (T-ALL) die from disease relapse due to low responses to standard chemotherapy and the lack of a targeted therapy that selectively eradicates the chemoresistant leukemia-initiating cells (LICs) responsible for disease recurrence. We reported recently that the reprogramming factor Krüppel-like factor 4 (KLF4) has a tumor-suppressive function in children with T-ALL...
May 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28464451/quantitative-phosphoproteome-analysis-of-cisplatin-induced-apoptosis-in-jurkat-t-cells
#7
The Trung Tran, Margarita Strozynski, Bernd Thiede
Protein phosphorylation is one of the most important posttranslational modifications (PTMs) due to its vital role in cellular functions and signaling pathways. Protein phosphorylation is also known to be involved in the regulation of apoptosis. Previously, we have performed a SILAC-based analysis of tyrosine phosphorylated peptides of cisplatin-induced apoptotic Jurkat T cells. Here, we analyzed the global phosphorylation profile by enrichment of serine/threonine/tyrosine phosphorylated peptides using TiO2 beads...
May 2, 2017: Proteomics
https://www.readbyqxmd.com/read/28371394/principles-and-approach-to-developing-mammalian-cell-culture-media-for-high-cell-density-perfusion-process-leveraging-established-fed-batch-media
#8
Henry Lin, Robert Woodrow Leighty, Scott Godfrey, Samantha Boran Wang
Perfusion medium was successfully developed based on our fed-batch platform basal and feed media. A systematic development approach was undertaken by first optimizing the ratios of fed-batch basal and feed media followed by targeted removal of unnecessary and redundant components. With this reduction in components, the medium could then be further concentrated by 2× to increase medium depth. The medium osmolality was also optimized where we found ∼360 mOsm/kg was desirable resulting in a residual culture osmolality of ∼300 mOsm/kg for our cell lines...
April 3, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28358847/alpha-1-antitrypsin-suppresses-oxidative-stress-in-preeclampsia-by-inhibiting-the-p38mapk-signaling-pathway-an-in-vivo-and-in-vitro-study
#9
Ya-Ling Feng, Yong-Xiang Yin, Jian Ding, Hua Yuan, Lan Yang, Jian-Juan Xu, Ling-Qin Hu
This present study was designed to investigate the effects of alpha-1-antitrypsin (AAT) on oxidative stress in preeclampsia (PE) by regulating p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. HTR8/SVneo cells were randomly assigned into normal, hypoxia/reoxygenation (H/R), HR + AAT and HR + siRNA-AAT groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expressions of p-p38MAPK, AAT, signal transducer and activator of transcription 1 (STAT1) and activating transcription factor2 (ATF2)...
2017: PloS One
https://www.readbyqxmd.com/read/28337266/long-non-coding-rna-uca1-promotes-cell-progression-by-acting-as-a-competing-endogenous-rna-of-atf2-in-prostate-cancer
#10
Shilong Zhang, Xinxin Dong, Tongyu Ji, Guoxiao Chen, Lei Shan
Prostate cancer (PCa) is a leading cause of cancer-related deaths in elder men. This disease has limited therapeutic options and poor prognosis as the underlying molecular mechanisms are not clearly understood. LncRNA UCA1 functions as an oncogene in many types of cancers. However, the role of UCA1 in PCa remains unclear. In the present study, we showed that UCA1 was significantly up-regulated in PCa cell lines and tissue samples. High UCA1 expression was positively associated with high gleason score, advanced TNM stage and shorter overall survival of PCa patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28318081/silencing-of-atf2-inhibits-growth-of-pancreatic-cancer-cells-and-enhances-sensitivity-to-chemotherapy
#11
Mu Li, Xingda Wu, Ning Liu, Xiaoying Li, Fanbin Meng, Shaowei Song
Pancreatic cancer is one of the leading causes of cancer-related death worldwide. Activating transcription factor 2 (ATF2) is a multifunctional transcription factor, and is implicated in tumor progress, yet its role in pancreatic cancer remains unclear. In the present study, the level of ATF2 in pancreatic cancer tissues and the adjacent non-tumorous tissues was detected by quantitative real-time PCR and Western blot. The roles of ATF2 in the proliferation, cell cycle, and apoptosis of pancreatic cancer cells were investigated through ATF2 silencing, and the effect of ATF2 shRNA on the sensitivity of pancreatic cancer cells to gemcitabine, an anti-tumor drug, was explored...
March 20, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28298358/identification-of-%C3%AE-catenin-interacting-proteins-in-nuclear-fractions-of-native-rat-collecting-duct-cells
#12
Jacqueline R Hwang, Chung-Lin Chou, Barbara Medvar, Mark A Knepper, Hyun Jun Jung
The gene encoding the aquaporin-2 water channel is regulated transcriptionally in response to vasopressin. In the renal collecting duct, vasopressin stimulates the nuclear translocation and phosphorylation (at Ser552) of β-catenin, a multifunctional protein that acts as a transcriptional co-regulator in the nucleus. The purpose of this study was to identify β-catenin interacting proteins that may be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells using both experimental and computational approaches...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28281638/mir-34a-5p-promotes-multi-chemoresistance-of-osteosarcoma-through-down-regulation-of-the-dll1-gene
#13
Youguang Pu, Fangfang Zhao, Haiyan Wang, Shanbao Cai
MiR-34a-5p has been implicated in the tumorigenesis and progression of several types of cancer. However, the role of miR-34a-5p in osteosarcoma (OS) remains largely unknown. This study was performed in two multi-chemosensitive (G-292 and MG63.2) and two resistant (SJSA-1 and MNNG/HOS) OS cell lines. MiR-34a-5p promotes OS multi-chemoresistance via its repression of the Delta-like ligand 1 (DLL1) gene, the ligand of the Notch pathway, and thus negatively correlates with OS chemoresistance. The siRNA-mediated repression of the DLL1 gene suppressed cell apoptosis and de-sensitized G-292 and MG63...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212892/atf2-a-paradigm-of-the-multifaceted-regulation-of-transcription-factors-in-biology-and-disease
#14
REVIEW
Gregory Watson, Ze'ev A Ronai, Eric Lau
Stringent transcriptional regulation is crucial for normal cellular biology and organismal development. Perturbations in the proper regulation of transcription factors can result in numerous pathologies, including cancer. Thus, understanding how transcription factors are regulated and how they are dysregulated in disease states is key to the therapeutic targeting of these factors and/or the pathways that they regulate. Activating transcription factor 2 (ATF2) has been studied in a number of developmental and pathological conditions...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28205618/ald5-pad1-atf1-and-atf2-facilitate-the-catabolism-of-coniferyl-aldehyde-ferulic-acid-and-p-coumaric-acid-in-saccharomyces-cerevisiae
#15
Peter Temitope Adeboye, Maurizio Bettiga, Lisbeth Olsson
The ability of Saccharomyces cerevisiae to catabolize phenolic compounds remains to be fully elucidated. Conversion of coniferyl aldehyde, ferulic acid and p-coumaric acid by S. cerevisiae under aerobic conditions was previously reported. A conversion pathway was also proposed. In the present study, possible enzymes involved in the reported conversion were investigated. Aldehyde dehydrogenase Ald5, phenylacrylic acid decarboxylase Pad1, and alcohol acetyltransferases Atf1 and Atf2, were hypothesised to be involved...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198054/regulation-of-atf1-and-atf2-transcripts-by-sequences-in-their-3-untranslated-region-in-cleavage-stage-cattle-embryos
#16
Ernesto Orozco-Lucero, Isabelle Dufort, Marc-André Sirard
The sequence of a 3' untranslated region (3'UTR) of mRNA governs the timing of its polyadenylation and translation in mammalian oocytes and early embryos. The objective of this study was to assess the influence of cis-elements in the 3'UTR of the developmentally important ATF1 and ATF2 transcripts on their timely translation during first cleavages in bovine embryos. Eight different reporter mRNAs (coding sequence of green fluorescent protein [GFP] fused to the 3'UTR of short or long isoforms of cattle ATF1 or -2, with or without polyadenylation) or a control GFP mRNA were microinjected separately into presumptive bovine zygotes at 18 hr post-insemination (hpi), followed by epifluorescence assessment for GFP translation between 24 and 80 hpi (expressed as percentage of GFP-positive embryos calculated from the total number of individuals)...
February 15, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28120035/the-role-of-nrf2-and-atf2-in-resistance-to-platinum-based-chemotherapy
#17
Jianli Chen, Charalambos Solomides, Fiona Simpkins, Henry Simpkins
PURPOSE: Nrf2 and its role in controlling levels of the AKR family of aldo-keto reductases which have been implicated in resistance to platinum-based chemotherapy was studied in ovarian, cervical and lung cell lines. METHODS: Nrf2 shRNA knockdowns of cells from different tumor origins were prepared to determine the role of this factor in producing resistance to platinum chemotherapy. RESULTS: Nrf2 knockdowns resulted in marked decreases in AKR1C1, AKR1C2 and to a lesser extent AKR1C3...
February 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28105187/atf2-translation-is-induced-under-chemotherapeutic-drug-mediated-cellular-stress-via-an-ires-dependent-mechanism-in-human-hepatic-cancer-bel7402-cells
#18
Qi Li, Wen-Qing Gao, Wen-Yan Dai, Chuang Yu, Rui-Yu Zhu, Jian Jin
Activating transcription factor (ATF) 2 is a member of the ATF/cyclic AMP-responsive element binding protein family, which exhibits both oncogenic and tumor-suppressor functions. In our preliminary experiments, it was observed that the expression of the ATF2 protein was induced following treatment with adriamycin (ADR) and paclitaxel (PTX), which may be regulated by internal ribosome entry segment (IRES)-mediated translation. By constructing a bicistronic vector containing the ATF2 5'-untranslated region (UTR), it was demonstrated that the ATF2 5'-UTR contains an IRES and maps a 30-nucleotide (nt) sequence (from nt 299 to nt ~269), which was essential for the IRES activity...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28013342/the-tlr4-nos1-ap1-signaling-axis-regulates-macrophage-polarization
#19
Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza Saqib Baig
OBJECTIVE: Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1-M2 phenotypes decides the nature, duration and severity of an inflammatory response. Although there is a substantial understanding of the fate of these phenotypes, the underlying molecular mechanism of transition within the M1-M2 phenotypes is not well understood. We have investigated the role of neuronal nitric oxide synthase (NOS1)-mediated regulation of activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change...
December 24, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27974798/mechanism-of-early-dissemination-and-metastasis-in-her2-mammary-cancer
#20
Kathryn L Harper, Maria Soledad Sosa, David Entenberg, Hedayatollah Hosseini, Julie F Cheung, Rita Nobre, Alvaro Avivar-Valderas, Chandandaneep Nagi, Nomeda Girnius, Roger J Davis, Eduardo F Farias, John Condeelis, Christoph A Klein, Julio A Aguirre-Ghiso
Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant. Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours. However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases. These findings, and those in pancreatic cancer and melanoma models, indicate that dissemination might occur during the early stages of tumour evolution...
December 14, 2016: Nature
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