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https://www.readbyqxmd.com/read/28441761/e2-er-%C3%AE-enhances-calcineurin-protein-degradation-and-pi3k-akt-mdm2-signal-transduction-to-inhibit-iso-induced-myocardial-cell-apoptosis
#1
Kuan-Ho Lin, Wei-Wen Kuo, Marthandam Asokan Shibu, Cecilia-Hsuan Day, You-Liang Hsieh, Li-Chin Chung, Ray-Jade Chen, Su-Ying Wen, Vijaya Padma Viswanadha, Chih-Yang Huang
Secretion of multifunctional estrogen and its receptor has been widely considered as the reason for markedly higher frequency of heart disease in men than in women. 17β-Estradiol (E2), for instance, has been reported to prevent development of cardiac apoptosis via activation of estrogen receptors (ERs). In addition, protein phosphatase such as protein phosphatase 1 (PP1) and calcineurin (PP2B) are also involved in cardiac hypertrophy and cell apoptosis signaling. However, the mechanism by which E2/ERβ suppresses apoptosis is not fully understood, and the role of protein phosphatase in E2/ERβ action also needs further investigation...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28435028/antagonistic-effects-of-p53-and-hif1a-on-microrna-34a-regulation-of-ppp1r11-and-stat3-and-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells
#2
Huihui Li, Matjaz Rokavec, Longchang Jiang, David Horst, Heiko Hermeking
BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides cancer cells with a selective advantage under conditions of hypoxia, but little is known about the mediators of this effect. METHODS: Isogenic CRC cell lines with different TP53 genotypes were placed under conditions of hypoxia. We examined the effects on levels and activity of microRNA-34 a (MIR34A) in CRC cells...
April 20, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28430823/modulation-the-alternative-splicing-of-gla-ivs4-919g-a-in-fabry-disease
#3
Wen-Hsin Chang, Dau-Ming Niu, Chi-Yu Lu, Shyr-Yi Lin, Ta-Chih Liu, Jan-Gowth Chang
While a base substitution in intron 4 of GLA (IVS4+919G>A) that causes aberrant alternative splicing resulting in Fabry disease has been reported, its molecular mechanism remains unclear. Here we reported that upon IVS4+919G>A transversion, H3K36me3 was enriched across the alternatively spliced region. PSIP1, an adapter of H3K36me3, together with Hsp70 and NONO were recruited and formed a complex with SF2/ASF and SRp20, which further promoted GLA splicing. Amiloride, a splicing regulator in cancer cells, could reverse aberrant histone modification patterns and disrupt the association of splicing complex with GLA...
2017: PloS One
https://www.readbyqxmd.com/read/28415748/the-spi1-pu-1-transcription-factor-accelerates-replication-fork-progression-by-increasing-pp1-phosphatase-in-leukemia
#4
Pauline Rimmelé, Michela Esposito, Laure Delestré, Jean-Hugues Guervilly, Maya Ridinger-Saison, Emmanuelle Despras, Françoise Moreau-Gachelin, Filippo Rosselli, Christel Guillouf
Oncogenes trigger replicative stress that can lead to genetic instability, which participates in cancer progression. Thus, determining how cells cope with replicative stress can help our understanding of oncogenesis and lead to the identification of new antitumor treatment targets. We previously showed that constitutive overexpression of the oncogenic transcription factor Spi1/PU.1 leads to pre-leukemic cells that have a shortened S phase duration with an increased replication fork speed and increased mutability in the absence of DNA breaks...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415724/pharmacological-inhibition-of-src-kinase-protects-against-acute-kidney-injury-in-a-murine-model-of-renal-ischemia-reperfusion
#5
Chongxiang Xiong, Xiujuan Zang, Xiaoxu Zhou, Lirong Liu, Monica V Masucci, Jinhua Tang, Xuezhu Li, Na Liu, George Bayliss, Ting C Zhao, Shougang Zhuang
Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387711/descriptive-analysis-of-lap1-distribution-and-that-of-associated-proteins-throughout-spermatogenesis
#6
Joana B Serrano, Filipa Martins, João C Sousa, Cátia D Pereira, Ans M M van Pelt, Sandra Rebelo, Odete A B da Cruz E Silva
Spermatogenesis comprises highly complex differentiation processes. Nuclear envelope (NE) proteins have been associated with these processes, including lamins, lamina-associated polypeptide (LAP) 2 and the lamin B-receptor. LAP1 is an important NE protein whose function has not been fully elucidated, but several binding partners allow predicting putative LAP1 functions. To date, LAP1 had not been associated with spermatogenesis. In this study, LAP1 expression and cellular/subcellular localization during spermatogenesis in human and mouse testes is established for the first time...
April 7, 2017: Membranes
https://www.readbyqxmd.com/read/28387646/unfair-competition-governs-the-interaction-of-pcpi-17-with-myosin-phosphatase-pp1-mypt1
#7
Joshua J Filter, Byron C Williams, Masumi Eto, David Shalloway, Michael L Goldberg
The small phosphoprotein pCPI-17 inhibits myosin light chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MCLP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP's active site...
April 7, 2017: ELife
https://www.readbyqxmd.com/read/28381458/protein-phosphatase-2c-pp2c-is-responsible-for-vp-induced-dephosphorylation-of-aqp2-serine-261
#8
Pui W Cheung, Lars Ueberdiek, Jack Day, Richard Bouley, Dennis Brown
AQP2 trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 c-terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in the phosphorylation of serine 256 (S256), S264 and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Only sanguinarine, a specific protein phosphatase 2C (PP2C) inhibitor, abolished VP-induced S261 dephosphorylation, but not inhibitors of PP1, PP2A (okadaic acid) or PP2B (cyclosporine)...
April 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28349036/monitoring-internal-training-load-and-salivary-immune-endocrine-responses-during-an-annual-judo-training-periodization
#9
Marcus F Agostinho, Alexandre Moreira, Ursula F Julio, Gilvan S Marcolino, Barbara M M Antunes, Fabio S Lira, Emerson Franchini
The objective of this study was to examine the internal training load (TL), IgA, and salivary steroid hormone responses in elite youth judo athletes during an entire annual training periodization. Ten male judo athletes (18±2 years, 72.3±12.3 kg, and 175±6 cm) competing at a state/national level were examined for the TL and salivary imune-endocrine responses variations over an annual judo season, divided in three macrocyles composed by distinct periods denominated preparatory period (PP), competitive period (CP) and transition period (TP)...
February 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/28337461/molecular-mechanism-for-the-regulation-of-microcystin-toxicity-to-protein-phosphatase-1-by-glutathione-conjugation-pathway
#10
Wansong Zong, Xiaoning Wang, Yonggang Du, Shuhan Zhang, Ying Zhang, Yue Teng
Glutathione (GSH) conjugation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases. To explore the specific molecular mechanism for GSH detoxification, two typical MC-GSHs (derived from MCLR and MCRR) were synthesized, prepared, and purified according to previous research. Then, the reduced inhibition effect for MC-GSHs on protein phosphatase 1 was verified by comparing with their original toxins. To further clarify the molecular mechanism for MC-GSHs detoxification, we evaluated the interactions between MCs/MC-GSHs and PP1 with the assistance of MOE molecule simulation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28330616/systematic-analysis-of-human-protein-phosphatase-interactions-and-dynamics
#11
Leena Yadav, Fitsum Tamene, Helka Göös, Audrey van Drogen, Riku Katainen, Ruedi Aebersold, Matthias Gstaiger, Markku Varjosalo
Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28319064/oct4-controls-mitotic-stability-and-inactivates-the-rb-tumor-suppressor-pathway-to-enhance-ovarian-cancer-aggressiveness
#12
E Comisso, M Scarola, M Rosso, S Piazza, S Marzinotto, Y Ciani, M Orsaria, L Mariuzzi, C Schneider, S Schoeftner, R Benetti
OCT4 (Octamer-binding transcription factor 4) is essential for embryonic stem cell self-renewal. Here we show that OCT4 increases the aggressiveness of high-grade serous ovarian cancer (HG-SOC) by inactivating the Retinoblastoma tumor suppressor pathway and enhancing mitotic stability in cancer cells. OCT4 drives the expression of Nuclear Inhibitor of Protein Phosphatase type 1 (NIPP1) and Cyclin F (CCNF) that together inhibit Protein Phosphatase 1 (PP1). This results in pRB hyper-phosphorylation, accelerated cell proliferation and increased in vitro tumorigenicity of ovarian cancer cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28297665/mitotic-phosphorylation-of-trex1-c-terminus-disrupts-trex1-regulation-of-the-oligosaccharyltransferase-complex
#13
Martin Kucej, Charles S Fermaintt, Kun Yang, Ricardo A Irizarry-Caro, Nan Yan
TREX1 mutations are associated with several autoimmune and inflammatory diseases. The N-terminal DNase domain of TREX1 is important for preventing self-DNA from activating the interferon response. The C terminus of TREX1 is required for ER localization and regulation of oligosacchariyltransferase (OST) activity. Here, we show that during mitosis TREX1 is predominately phosphorylated at the C-terminal Serine-261 by Cyclin B/CDK1. TREX1 is dephosphorylated quickly at mitotic exit, likely by PP1/PP2-type serine/threonine phosphatase...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296156/pai1-a-novel-pp1-interacting-protein-that-mediates-human-plasma-s-anti-apoptotic-effect-in-endothelial-cells
#14
Hui Yao, Guangchun He, Chao Chen, Shichao Yan, Lu Lu, Liujiang Song, K Vinod Vijayan, Qinglong Li, Li Xiong, Xiongying Miao, Xiyun Deng
Activation of apoptotic signalling in endothelial cells contributes to the detrimental effects of a variety of pathological stimuli. In investigating the molecular events underlying the anti-apoptotic effect of human plasma in cultured human endothelial cells, we unexpectedly uncovered a novel mechanism of apoptosis suppression by human plasma through an interaction between two previously unrelated proteins. Human plasma inhibited hypoxia-serum deprivation-induced apoptosis and stimulated BAD(S136) and Akt(S473) phosphorylation...
March 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28283191/ccdc181-is-a-microtubule-binding-protein-that-interacts-with-hook1-in-haploid-male-germ-cells-and-localizes-to-the-sperm-tail-and-motile-cilia
#15
Thomas Schwarz, Barbara Prieler, Johannes A Schmid, Pawel Grzmil, Juergen Neesen
Disruption of murine Hook1 results in a disturbed spermatogenesis and consequently leads to male infertility in mice. Within these mice abnormal sperm development starts with a disorganization of the microtubular manchette in elongating spermatids that leads to an abnormal head shape as well as to distinctive structural changes in the flagella of the sperm. To elucidate Hook1 function in male germ cell differentiation a yeast two-hybrid screen was performed using a murine testicular library, which leads to the identification of several putative Hook1 interacting proteins...
February 20, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28276587/phosphoregulation-of-k-cl-cotransporters-during-cell-swelling-novel-insights
#16
Rachelle Frenette-Cotton, Andrée-Anne Marcoux, Alexandre P Garneau, Micheline Noel, Paul Isenring
The K(+) -Cl(-) cotransporters (KCCs) belong to the cation-Cl(-) cotransporter family and consist of 4 isoforms and many splice variants. Their main role is to promote electroneutral efflux of K(+) and Cl(-) ions across the surface of many cell types and, thereby, to regulate intracellular ion concentration, cell volume and epithelial salt movement. These transport systems are induced by an increase in cell volume and are less active at lower intracellular [Cl(-) ] (Cli ), but the mechanisms at play are still ill-defined...
March 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28273463/reversal-of-ddk-mediated-mcm-phosphorylation-by-rif1-pp1-regulates-replication-initiation-and-replisome-stability-independently-of-atr-chk1
#17
Robert C Alver, Gaganmeet Singh Chadha, Peter J Gillespie, J Julian Blow
Dbf4-dependent kinases (DDKs) are required for the initiation of DNA replication, their essential targets being the MCM2-7 proteins. We show that, in Xenopus laevis egg extracts and human cells, hyper-phosphorylation of DNA-bound Mcm4, but not phosphorylation of Mcm2, correlates with DNA replication. These phosphorylations are differentially affected by the DDK inhibitors PHA-767491 and XL413. We show that DDK-dependent MCM phosphorylation is reversed by protein phosphatase 1 (PP1) targeted to chromatin by Rif1...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28250012/innate-immunity-to-rna-virus-is-regulated-by-temporal-and-reversible-sumoylation-of-rig-i-and-mda5
#18
Ming-Ming Hu, Chen-Yang Liao, Qing Yang, Xue-Qin Xie, Hong-Bing Shu
Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I-mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells...
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28202662/biogenesis-and-activity-regulation-of-protein-phosphatase-1
#19
REVIEW
Iris Verbinnen, Monica Ferreira, Mathieu Bollen
Protein phosphatase 1 (PP1) is expressed in all eukaryotic cells and catalyzes a substantial fraction of phosphoserine/threonine dephosphorylation reactions. It forms stable complexes with PP1-interacting proteins (PIPs) that guide the phosphatase throughout its life cycle and control its fate and function. The diversity of PIPs is huge (≈200 in vertebrates), and most of them combine short linear motifs to form large and unique interaction interfaces with PP1. Many PIPs have separate domains for PP1 anchoring, PP1 regulation, substrate recruitment and subcellular targeting, which enable them to direct associated PP1 to a specific subset of substrates and mediate acute activity control...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28189088/identification-of-residues-within-the-african-swine-fever-virus-dp71l-protein-required-for-dephosphorylation-of-translation-initiation-factor-eif2%C3%AE-and-inhibiting-activation-of-pro-apoptotic-chop
#20
Claire Barber, Chris Netherton, Lynnette Goatley, Alice Moon, Steve Goodbourn, Linda Dixon
The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required...
April 2017: Virology
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