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https://www.readbyqxmd.com/read/28319064/oct4-controls-mitotic-stability-and-inactivates-the-rb-tumor-suppressor-pathway-to-enhance-ovarian-cancer-aggressiveness
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
March 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28202662/biogenesis-and-activity-regulation-of-protein-phosphatase-1
#8
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
#9
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
https://www.readbyqxmd.com/read/28188792/recruitment-of-pp1-to-the-centrosomal-scaffold-protein-cep192
#10
Isha Nasa, Laura Trinkle-Mulcahy, P Douglas, Sibapriya Chaudhuri, S P Lees-Miller, Kyung S Lee, Greg B Moorhead
Centrosomal protein of 192 kDa (CEP192) is a scaffolding protein that recruits the mitotic protein kinases Aurora A and PLK1 to the centrosome. Here we demonstrate that CEP192 also recruits the type one protein phosphatase (PP1) via a highly conserved KHVTF docking motif. The threonine of the KHVTF motif is phosphorylated during mitosis and protein kinase inhibition studies suggest this to be a PLK1-dependent process.
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28176357/bri2-processing-and-its-neuritogenic-role-are-modulated-by-protein-phosphatase-1-complexing
#11
Filipa Martins, Joana B Serrano, T Müller, Odete A B da Cruz E Silva, Sandra Rebelo
BRI2 is a ubiquitously expressed type-II transmembrane phosphoprotein. BRI2 undergoes proteolytic processing into secreted fragments and during the maturation process it suffers post-translational modifications. Of particular relevance, BRI2 is a protein phosphatase 1 (PP1) interacting protein, where PP1 is able to dephosphorylate the former. Further, disruption of the BRI2:PP1 complex, using BRI2 PP1 binding motif mutants, leads to increased BRI2 phosphorylation levels. However, the physiological function of BRI2 remains elusive; although findings suggest a role in neurite outgrowth and neuronal differentiation...
February 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28163251/overexpression-of-carboxylesterase-contributes-to-the-attenuation-of-cyanotoxin-microcystin-lr-toxicity
#12
Shota Takumi, Tai Shimono, Satoshi Ikema, Yuki Hotta, Petros K Chigwechokha, Kazuhiro Shiozaki, Yasumasa Sugiyama, Mitsuru Hashimoto, Tatsuhiko Furukawa, Masaharu Komatsu
Microcystin-LR is a hepatotoxin produced by several cyanobacteria. Its toxicity is mainly due to a inhibition of protein phosphatase, PP1 and PP2A. Previously, we used a cell line stably expressing uptake transporter for microcystin-LR, OATP1B3 (HEK293-OATP1B3 cells). In this study, to determine whether overexpression of carboxylesterase (CES), which degrades ester-group and amide-group, attenuates the cytotoxicity of microcystin-LR, we generated the HEK293-OATP1B3/CES2 double-transfected cells. HEK293-OATP1B3/CES2 cells showed high hydrolysis activity of p-nitrophenyl acetate (PNPA), which is an authentic substrate for esterase...
April 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28152298/salubrinal-alleviates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-endoplasmic-reticulum-stress-pathway
#13
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Chunghee Cho, Do Han Kim
Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs)...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#14
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28134629/liguzinediol-enhances-the-inotropic-effect-of-rat-hearts-via-inhibition-of-protein-phosphatase-pp1-and-pp2a-activities
#15
Sha Li, Huili Huang, Mengdan Zhang, Wei Wang, Shuyin Xue, Ying Gao, Ming Xie, Kesu Chen, Fuming Liu, Long Chen
It has been demonstrated that Liguzinediol (LZDO), a derivative of ligustrazine from ligusticum wallichii Franch, exerts positive inotropy in isolated rat heart mediated by the sarcoplasmic reticulum Ca-ATPase (SERCA2a). Here, we further explore the underlying mechanism of the positive inotropic effect of LZDO in rat hearts. In vivo and ex vivo rat heart experiments, biochemistry and Western blot techniques were used to analyze the rat heart contractility, SERCA2a activity, phospholamban (PLB) phosphorylation and protein phosphatase (PP1 and PP2A) activities in rat left ventricular myocytes, respectively...
January 27, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28131631/ryanodine-receptor-modification-and-regulation-by-intracellular-ca-2-and-mg-2-in-healthy-and-failing-human-hearts
#16
K Walweel, P Molenaar, M S Imtiaz, A Denniss, C Dos Remedios, D F van Helden, A F Dulhunty, D R Laver, N A Beard
RATIONALE: Heart failure is a multimodal disorder, of which disrupted Ca(2+) homeostasis is a hallmark. Central to Ca(2+) homeostasis is the major cardiac Ca(2+) release channel - the ryanodine receptor (RyR2) - whose activity is influenced by associated proteins, covalent modification and by Ca(2+) and Mg(2+). That RyR2 is remodelled and its function disturbed in heart failure is well recognized, but poorly understood. OBJECTIVE: To assess Ca(2+) and Mg(2+) regulation of RyR2 from left ventricles of healthy, cystic fibrosis and failing hearts, and to correlate these functional changes with RyR2 modifications and remodelling...
March 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28131630/the-effect-of-pka-mediated-phosphorylation-of-ryanodine-receptor-on-sr-ca-2-leak-in-ventricular-myocytes
#17
Elisa Bovo, Sabine Huke, Lothar A Blatter, Aleksey V Zima
Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca(2+) release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca(2+)] and intra-SR [Ca(2+)]SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies...
March 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28126489/the-protein-serine-threonine-phosphatases-pp2a-pp1-and-calcineurin-a-triple-threat-in-the-regulation-of-the-neuronal-cytoskeleton
#18
REVIEW
Alexander Hoffman, Goce Taleski, Estelle Sontag
The microtubule, F-actin and neurofilament networks play a critical role in neuronal cell morphogenesis, polarity and synaptic plasticity. Significantly, the assembly/disassembly and stability of these cytoskeletal networks is crucially modulated by protein phosphorylation and dephosphorylation events. Herein, we aim to more closely examine the role played by three major neuronal Ser/Thr protein phosphatases, PP2A, PP1 and calcineurin, in the homeostasis of the neuronal cytoskeleton. There is strong evidence that these enzymes interact with and dephosphorylate a variety of cytoskeletal proteins, resulting in major regulation of neuronal cytoskeletal dynamics...
January 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28103229/protein-phosphatase-1-down-regulates-zyg-1-levels-to-limit-centriole-duplication
#19
Nina Peel, Jyoti Iyer, Anar Naik, Michael P Dougherty, Markus Decker, Kevin F O'Connell
In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2SZY-2 and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation of szy-2 or sds-22 can rescue the loss of centriole duplication associated with a zyg-1 hypomorphic allele...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28102742/the-nucleoporin-mel-28-elys-a-pp1-scaffold-during-m-phase-exit
#20
Neil Hattersley, Arshad Desai
No abstract text is available yet for this article.
January 19, 2017: Cell Cycle
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