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[PMID]:28743746
[Au] Autor:Citterio CE; Veluswamy B; Morgan SJ; Galton VA; Banga JP; Atkins S; Morishita Y; Neumann S; Latif R; Gershengorn MC; Smith TJ; Arvan P
[Ad] Endereço:From the Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan 48105.
[Ti] Título: triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.
[So] Source:J Biol Chem;292(37):15434-15444, 2017 09 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The thyroid gland secretes primarily tetraiodothyronine (T ), and some triiodothyronine (T ). Under normal physiological circumstances, only one-fifth of circulating T is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T toxicosis. Thyroidal T production results from iodination of thyroglobulin (TG) at residues Tyr and Tyr , whereas thyroidal T production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T is formed independently of deiodination from T We found that upon iodination , T formation in TG was decreased in mice lacking TSHRs. Conversely, T that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced T formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T upon iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances T formation, contributing to the relative T toxicosis of Graves' disease.
[Mh] Termos MeSH primário: Processamento de Proteína Pós-Traducional
Receptores da Tireotropina/agonistas
Transdução de Sinais
Tireoglobulina/metabolismo
Células Epiteliais da Tireóide/metabolismo
Tireotropina/metabolismo
Tri-Iodotironina/biossíntese
[Mh] Termos MeSH secundário: Animais
Proteínas de Ligação ao Cálcio/agonistas
Proteínas de Ligação ao Cálcio/genética
Proteínas de Ligação ao Cálcio/metabolismo
Caseína Quinase I/genética
Caseína Quinase I/metabolismo
Linhagem Celular
Células Cultivadas
Proteínas da Matriz Extracelular/agonistas
Proteínas da Matriz Extracelular/genética
Proteínas da Matriz Extracelular/metabolismo
Doença de Graves/sangue
Doença de Graves/metabolismo
Doença de Graves/patologia
Halogenação
Seres Humanos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fosforilação
Proteínas Serina-Treonina Quinases/química
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Ratos
Receptores da Tireotropina/genética
Receptores da Tireotropina/metabolismo
Tireoglobulina/secreção
Células Epiteliais da Tireóide/citologia
Células Epiteliais da Tireóide/patologia
Células Epiteliais da Tireóide/secreção
Tirosina/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Calcium-Binding Proteins); 0 (Extracellular Matrix Proteins); 0 (FAM20C protein, mouse); 0 (Receptors, Thyrotropin); 06LU7C9H1V (Triiodothyronine); 42HK56048U (Tyrosine); 9002-71-5 (Thyrotropin); 9010-34-8 (Thyroglobulin); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (FAM20C protein, human); EC 2.7.11.1 (Fam20C protein, rat); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.784447


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[PMID]:28988058
[Au] Autor:Zhang L; Li H; Chen Y; Gao X; Lu Z; Gao L; Wang Y; Gao Y; Gao H; Liu C; Cui H; Zhang Y; Pan Q; Qi X; Wang X
[Ad] Endereço:Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
[Ti] Título:The down-regulation of casein kinase 1 alpha as a host defense response against infectious bursal disease virus infection.
[So] Source:Virology;512:211-221, 2017 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Infectious bursal disease virus (IBDV) is an important immunosuppressive virus of chickens. Although the gene functions of IBDV have been well characterized, the host responses during IBDV infection remain much poor. In the present study, casein kinase 1 alpha (CK1α), a novel VP2-associated protein, was down-regulated during IBDV replication in DF1 cells. Further experiments showed that siRNA-mediated knockdown of CK1α inhibited IBDV replication, while overexpression of CK1α promoted IBDV growth. Finally, we revealed that the effects of CK1α expression level on IBDV replication were involved in the negative regulation of CK1α on type I interferon receptor (IFNAR1), because ubiquitination assay analyses demonstrated that CK1α could promote the ubiquitination of IFNAR1, thereby affecting the stability of this receptor. In conclusion, down-regulation of CK1α during IBDV infection as a host defense response increased abundance of IFNAR1, which in turn enhanced an inhibitory effect on IBDV replication.
[Mh] Termos MeSH primário: Caseína Quinase I/metabolismo
Fibroblastos/metabolismo
Regulação Enzimológica da Expressão Gênica/imunologia
Vírus da Doença Infecciosa da Bursa/fisiologia
[Mh] Termos MeSH secundário: Animais
Caseína Quinase I/genética
Linhagem Celular
Embrião de Galinha
Regulação para Baixo
Ligação Proteica
Receptor de Interferon alfa e beta/genética
Receptor de Interferon alfa e beta/metabolismo
Proteínas Estruturais Virais/genética
Proteínas Estruturais Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (VP2 protein, infectious bursal disease virus); 0 (Viral Structural Proteins); 156986-95-7 (Receptor, Interferon alpha-beta); EC 2.7.11.1 (Casein Kinase I)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


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[PMID]:28793293
[Au] Autor:Al Mamun Bhuyan A; Cao H; Lang F
[Ad] Endereço:Department of Internal Medicine III, Tuebingen, Germany.
[Ti] Título:Triggering of Eryptosis, the Suicidal Erythrocyte Death by Mammalian Target of Rapamycin (mTOR) inhibitor Temsirolimus.
[So] Source:Cell Physiol Biochem;42(4):1575-1591, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is utilized for the treatment of malignancy. Temsirolimus is at least in part effective by triggering suicidal tumor cell death. The most common side effect of temsirolimus treatment is anemia. At least in theory, the anemia following temsirolimus treatment could result from stimulation of eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the orchestration of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, as well as activation of staurosporine and chelerythrine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases. The purpose of the present study was to test whether temsirolimus influences eryptosis and, if so, to shed light on the signaling involved. METHODS: Flow cytometry was employed to estimate cell volume from forward scatter, phosphatidylserine exposure at the cell surface from annexin-V-binding, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was determined from hemoglobin concentration in the supernatant. RESULTS: A 48 hours exposure of human erythrocytes to temsirolimus (5 - 20 µg/ml) significantly decreased forward scatter and significantly increased the percentage of annexin-V-binding cells. Temsirolimus significantly increased Fluo3-fluorescence, DCFDA fluorescence and ceramide abundance at the erythrocyte surface. The effect of temsirolimus on annexin-V-binding was significantly blunted but not abolished by removal of extracellular Ca2+ and by addition of staurosporine (1 µM) or chelerythrine (10 µM) but not significantly modified by addition of SB203580 (2 µM), D4476 (10 µM), or zVAD (10 µM). Chelerythrine (10 µM) further significantly blunted the effect of temsirolimus on DCFDA fluorescence but not ceramide formation. Removal of extracellular Ca2+ had no effect on temsirolimus induced ROS formation or ceramide abundance. CONCLUSIONS: Temsirolimus triggers eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca2+ entry, oxidative stress, ceramide and activation of staurosporine/Chelerythrine sensitive kinase(s).
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Eriptose/efeitos dos fármacos
Eritrócitos/efeitos dos fármacos
Hemólise/efeitos dos fármacos
Inibidores de Proteínas Quinases/farmacologia
Sirolimo/análogos & derivados
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Mh] Termos MeSH secundário: Compostos de Anilina/química
Anexina A5/metabolismo
Benzamidas/farmacologia
Benzofenantridinas/farmacologia
Cálcio/metabolismo
Caseína Quinase I/antagonistas & inibidores
Caseína Quinase I/genética
Caseína Quinase I/metabolismo
Caspases/genética
Caspases/metabolismo
Ceramidas/metabolismo
Eriptose/genética
Eritrócitos/citologia
Eritrócitos/metabolismo
Fluoresceínas/química
Regulação da Expressão Gênica
Seres Humanos
Imidazóis/farmacologia
Oligopeptídeos/farmacologia
Fosfatidilserinas/metabolismo
Cultura Primária de Células
Piridinas/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Transdução de Sinais
Sirolimo/farmacologia
Estaurosporina/farmacologia
Serina-Treonina Quinases TOR/genética
Serina-Treonina Quinases TOR/metabolismo
Xantenos/química
Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
Proteínas Quinases p38 Ativadas por Mitógeno/genética
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-(4-(2,3-dihydrobenzo(1,4)dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide); 0 (Aniline Compounds); 0 (Annexin A5); 0 (Antineoplastic Agents); 0 (Benzamides); 0 (Benzophenanthridines); 0 (Ceramides); 0 (Fluoresceins); 0 (Imidazoles); 0 (Oligopeptides); 0 (Phosphatidylserines); 0 (Protein Kinase Inhibitors); 0 (Pyridines); 0 (Reactive Oxygen Species); 0 (Xanthenes); 0 (benzyloxycarbonyl-valyl-alanyl-aspartic acid); 2044-85-1 (diacetyldichlorofluorescein); 23D4W0B50Y (Fluo-3); 624KN6GM2T (temsirolimus); E3B045W6X0 (chelerythrine); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.4.22.- (Caspases); H88EPA0A3N (Staurosporine); OU13V1EYWQ (SB 203580); SY7Q814VUP (Calcium); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1159/000479398


  4 / 418 MEDLINE  
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[PMID]:28424168
[Au] Autor:Li X; He L; Yue Q; Lu J; Kang N; Xu X; Wang H; Zhang H
[Ad] Endereço:Department of Cell Biology, Medical College of Soochow University, Jiangsu Key Laboratory of Stem Cell Research, Suzhou, China.
[Ti] Título:MiR-9-5p promotes MSC migration by activating ß-catenin signaling pathway.
[So] Source:Am J Physiol Cell Physiol;313(1):C80-C93, 2017 Jul 01.
[Is] ISSN:1522-1563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3ß, two inhibitors of ß-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated ß-catenin signaling pathway. In line with these data, inhibition of ß-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of ß-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating ß-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p.
[Mh] Termos MeSH primário: Células Mesenquimais Estromais/metabolismo
MicroRNAs/genética
Neurônios/metabolismo
beta Catenina/genética
[Mh] Termos MeSH secundário: Actinas/genética
Actinas/metabolismo
Animais
Caseína Quinase I/genética
Caseína Quinase I/metabolismo
Diferenciação Celular/efeitos dos fármacos
Movimento Celular/efeitos dos fármacos
Adesões Focais/efeitos dos fármacos
Adesões Focais/metabolismo
Regulação da Expressão Gênica
Glicogênio Sintase Quinase 3 beta/genética
Glicogênio Sintase Quinase 3 beta/metabolismo
Fator de Crescimento de Hepatócito/farmacologia
Cloreto de Lítio/farmacologia
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/efeitos dos fármacos
MicroRNAs/metabolismo
Neurônios/citologia
Neurônios/efeitos dos fármacos
Cultura Primária de Células
Ratos
Ratos Sprague-Dawley
Transdução de Sinais
Sulfonamidas/farmacologia
Transfecção
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Ctnnb1 protein, rat); 0 (FH535); 0 (MIRN9 microRNA, rat); 0 (MicroRNAs); 0 (Sulfonamides); 0 (beta Catenin); 67256-21-7 (Hepatocyte Growth Factor); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); G4962QA067 (Lithium Chloride)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170802
[Lr] Data última revisão:
170802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1152/ajpcell.00232.2016


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[PMID]:28360132
[Au] Autor:Sanial M; Bécam I; Hofmann L; Behague J; Argüelles C; Gourhand V; Bruzzone L; Holmgren RA; Plessis A
[Ad] Endereço:Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris F-75205, France.
[Ti] Título:Dose-dependent transduction of Hedgehog relies on phosphorylation-based feedback between the G-protein-coupled receptor Smoothened and the kinase Fused.
[So] Source:Development;144(10):1841-1850, 2017 05 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Smoothened (SMO) is a G-protein-coupled receptor-related protein required for the transduction of Hedgehog (HH). The HH gradient leads to graded phosphorylation of SMO, mainly by the PKA and CKI kinases. How thresholds in HH morphogen regulate SMO to promote switch-like transcriptional responses is a central unsolved issue. Using the wing imaginal disc model in , we identified new SMO phosphosites that enhance the effects of the PKA/CKI kinases on SMO accumulation, its localization at the plasma membrane and its activity. Surprisingly, phosphorylation at these sites is induced by the kinase Fused (FU), a known downstream effector of SMO. In turn, activation of SMO induces FU to act on its downstream targets. Overall, our data provide evidence for a SMO/FU positive regulatory loop nested within a multikinase phosphorylation cascade. We propose that this complex interplay amplifies signaling above a threshold that allows high HH signaling.
[Mh] Termos MeSH primário: Caseína Quinase I/metabolismo
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster
Proteínas Hedgehog/metabolismo
Proteínas Recombinantes de Fusão/metabolismo
Receptor Smoothened/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Caseína Quinase I/genética
Membrana Celular/metabolismo
Proteínas Quinases Dependentes de AMP Cíclico/genética
Proteínas de Drosophila/genética
Drosophila melanogaster/embriologia
Drosophila melanogaster/genética
Drosophila melanogaster/metabolismo
Proteínas Hedgehog/genética
Fosforilação
Proteínas Serina-Treonina Quinases/genética
Proteínas Serina-Treonina Quinases/metabolismo
Receptores Acoplados a Proteínas-G/genética
Receptores Acoplados a Proteínas-G/metabolismo
Proteínas Recombinantes de Fusão/genética
Transdução de Sinais
Receptor Smoothened/genética
Asas de Animais/embriologia
Asas de Animais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Hedgehog Proteins); 0 (Receptors, G-Protein-Coupled); 0 (Recombinant Fusion Proteins); 0 (Smoothened Receptor); 0 (smoothened protein, Drosophila); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1242/dev.144782


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[PMID]:28236970
[Au] Autor:Jiang J
[Ad] Endereço:University of Texas Southwestern Medical Center at Dallas, Dallas, TX, United States. Electronic address: jin.jiang@utsouthwestern.edu.
[Ti] Título:CK1 in Developmental Signaling: Hedgehog and Wnt.
[So] Source:Curr Top Dev Biol;123:303-329, 2017.
[Is] ISSN:1557-8933
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The casein kinase 1 (CK1) family of serine (Ser)/threonine (Thr) protein kinases participates in a myriad of cellular processes including developmental signaling. Hedgehog (Hh) and Wnt pathways are two major and evolutionarily conserved signaling pathways that control embryonic development and adult tissue homeostasis. Deregulation of these pathways leads to many human disorders including birth defects and cancer. Here, I review the role of CK1 in the regulation of Hh and Wnt signal transduction cascades from the membrane reception systems to the transcriptional effectors. In both Hh and Wnt pathways, multiple CK1 family members regulate signal transduction at several levels of the pathways and play either positive or negative roles depending on the signaling status, individual CK1 isoforms involved, and the specific substrates they phosphorylate. A common mechanism underlying the control of CK1-mediated phosphorylation of Hh and Wnt pathway components is the regulation of CK1/substrate interaction within large protein complexes. I will highlight this feature in the context of Hh signaling and draw interesting parallels between the Hh and Wnt pathways.
[Mh] Termos MeSH primário: Caseína Quinase I/metabolismo
Desenvolvimento Embrionário
Proteínas Hedgehog/metabolismo
Transdução de Sinais
Proteínas Wnt/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Seres Humanos
Via de Sinalização Wnt
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Hedgehog Proteins); 0 (Wnt Proteins); EC 2.7.11.1 (Casein Kinase I)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170227
[St] Status:MEDLINE


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[PMID]:28236661
[Au] Autor:Cozza G; Salvi M; Tagliabracci VS; Pinna LA
[Ad] Endereço:Department of Biomedical Sciences and CNR, Institute of Neuroscience, University of Padova, Italy.
[Ti] Título:Fam20C is under the control of sphingolipid signaling in human cell lines.
[So] Source:FEBS J;284(8):1246-1257, 2017 Apr.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Fam20C, also termed DMP-4 (dentin matrix protein 4) and G-CK (Golgi casein kinase) is an atypical protein kinase committed with the phosphorylation of casein and a plethora of other secreted proteins. Fam20C has been implicated in a number of human pathologies related to biomineralization, phosphate homeostasis, and neoplasia. The mode of regulation of Fam20C is still a matter of conjecture. In in vitro, Fam20C activity is stimulated several fold by sphingosine. To gain in vivo information about the physiological relevance of this observation, three cell lines expressing endogenous Fam20C, and one in which Fam20C has been knocked out with CRISPR/Cas9 technology have been examined for Fam20C activity under basal conditions and where sphingosine has been depleted by treatment with myriocin. In lysates and conditioned medium of the three wild-type cells, Fam20C activity was similar and comparably responsive to sphingosine and a panel of sphingosine analogs, while in knockout cells, Fam20C activity was undetectable either with or without sphingosine addition. Upon depletion of endogenous sphingosine by myriocin treatment, Fam20C activity drops to negligible values both in the lysate and in the conditioned medium; however, it can be partially restored if during myriocin treatment cells are supplemented with either exogenous sphingosine or ceramide, a sphingosine precursor. Alterations of Fam20C activity, promoted by myriocin and sphingolipids, are not accompanied by any significant change in Fam20C protein. These data provide the proof of concept that Fam20C activity is under the control of sphingolipid signaling.
[Mh] Termos MeSH primário: Caseína Quinase I/metabolismo
Proteínas da Matriz Extracelular/metabolismo
Esfingolipídeos/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Extracellular Matrix Proteins); 0 (Recombinant Proteins); 0 (Sphingolipids); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (FAM20C protein, human)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14052


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[PMID]:28125685
[Au] Autor:Greer YE; Gao B; Yang Y; Nussenzweig A; Rubin JS
[Ad] Endereço:Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland, United States of America.
[Ti] Título:Lack of Casein Kinase 1 Delta Promotes Genomic Instability - The Accumulation of DNA Damage and Down-Regulation of Checkpoint Kinase 1.
[So] Source:PLoS One;12(1):e0170903, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Casein kinase 1 delta (CK1δ) is a conserved serine/threonine protein kinase that regulates diverse cellular processes. Mice lacking CK1δ have a perinatal lethal phenotype and typically weigh 30% less than their wild type littermates. However, the causes of death and small size are unknown. We observed cells with abnormally large nuclei in tissue from Csnk1d null embryos, and multiple centrosomes in mouse embryo fibroblasts (MEFs) deficient in CK1δ (MEFCsnk1d null). Results from γ-H2AX staining and the comet assay demonstrated significant DNA damage in MEFCsnk1d null cells. These cells often contain micronuclei, an indicator of genomic instability. Similarly, abrogation of CK1δ expression in control MEFs stimulated micronuclei formation after doxorubicin treatment, suggesting that CK1δ loss increases vulnerability to genotoxic stress. Cellular levels of total and activated checkpoint kinase 1 (Chk1), which functions in the DNA damage response and mitotic checkpoints, and its downstream effector, Cdc2/CDK1 kinase, were often decreased in MEFCsnk1d null cells as well as in control MEFs transfected with CK1δ siRNA. Hydroxyurea-induced Chk1 activation, as measured by Ser345 phosphorylation, and nuclear localization also were impaired in MEF cells following siRNA knockdown of CK1δ. Similar results were observed in the MCF7 human breast cancer cell line. The decreases in phosphorylated Chk1 were rescued by concomitant expression of siRNA-resistant CK1δ. Experiments with cycloheximide demonstrated that the stability of Chk1 protein was diminished in cells subjected to CK1δ knockdown. Together, these findings suggest that CK1δ contributes to the efficient repair of DNA damage and the proper functioning of mitotic checkpoints by maintaining appropriate levels of Chk1.
[Mh] Termos MeSH primário: Caseína Quinase I/genética
Quinase do Ponto de Checagem 1/genética
Dano ao DNA
Regulação para Baixo
Instabilidade Genômica
[Mh] Termos MeSH secundário: Animais
Caseína Quinase I/metabolismo
Linhagem Celular Tumoral
Quinase do Ponto de Checagem 1/metabolismo
Fibroblastos/metabolismo
Seres Humanos
Camundongos
Camundongos Knockout
Mitose/genética
Fosforilação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (Checkpoint Kinase 1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170903


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[PMID]:28099937
[Au] Autor:Manni S; Carrino M; Manzoni M; Gianesin K; Nunes SC; Costacurta M; Tubi LQ; Macaccaro P; Taiana E; Cabrelle A; Barilà G; Martines A; Zambello R; Bonaldi L; Trentin L; Neri A; Semenzato G; Piazza F
[Ad] Endereço:Department of Medicine, Hematology and Clinical Immunology Section, University of Padova, Padova, Italy.
[Ti] Título:Inactivation of CK1α in multiple myeloma empowers drug cytotoxicity by affecting AKT and ß-catenin survival signaling pathways.
[So] Source:Oncotarget;8(9):14604-14619, 2017 Feb 28.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells. We demonstrated that CK1α inactivation, while toxic for myeloma cells, is dispensable for the survival of healthy B lymphocytes and stromal cells. Disruption of CK1α function in myeloma cells resulted in decreased Mdm2, increased p53 and p21 and reduced expression of ß-catenin and AKT. These effects were mediated partially by p53 and caspase activity. Finally, we discovered that CK1α inactivation enhanced the cytotoxic effect of both bortezomib and lenalidomide. Overall, our study supports a role for CK1α as a potential therapeutic target in MM in combination with proteasome inhibitors and/or immunomodulatory drugs.
[Mh] Termos MeSH primário: Caseína Quinase I/genética
Mieloma Múltiplo/genética
Proteínas Proto-Oncogênicas c-akt/genética
Transdução de Sinais/genética
beta Catenina/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/farmacologia
Bortezomib/farmacologia
Caseína Quinase I/metabolismo
Linhagem Celular
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/genética
Células Cultivadas
Inibidor de Quinase Dependente de Ciclina p21/genética
Inibidor de Quinase Dependente de Ciclina p21/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Masculino
Meia-Idade
Mieloma Múltiplo/metabolismo
Mieloma Múltiplo/patologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Proteínas Proto-Oncogênicas c-mdm2/genética
Proteínas Proto-Oncogênicas c-mdm2/metabolismo
Interferência de RNA
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Transdução de Sinais/efeitos dos fármacos
Talidomida/análogos & derivados
Talidomida/farmacologia
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (Tumor Suppressor Protein p53); 0 (beta Catenin); 4Z8R6ORS6L (Thalidomide); 69G8BD63PP (Bortezomib); EC 2.3.2.27 (MDM2 protein, human); EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); F0P408N6V4 (lenalidomide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.14654


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[PMID]:28017619
[Au] Autor:Argüello-Miranda O; Zagoriy I; Mengoli V; Rojas J; Jonak K; Oz T; Graf P; Zachariae W
[Ad] Endereço:Laboratory of Chromosome Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
[Ti] Título:Casein Kinase 1 Coordinates Cohesin Cleavage, Gametogenesis, and Exit from M Phase in Meiosis II.
[So] Source:Dev Cell;40(1):37-52, 2017 Jan 09.
[Is] ISSN:1878-1551
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A. Second, Hrr25 initiates the sporulation program by inducing the synthesis of membranes that engulf the emerging nuclei at anaphase II. Third, Hrr25 mediates exit from meiosis II by activating pathways that trigger the destruction of M-phase-promoting kinases. Thus, Hrr25 synchronizes formation of the single-copy genome with gamete differentiation and termination of meiosis.
[Mh] Termos MeSH primário: Caseína Quinase I/metabolismo
Proteínas de Ciclo Celular/metabolismo
Proteínas Cromossômicas não Histona/metabolismo
Gametogênese
Meiose
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/citologia
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Anáfase
Núcleo Celular/metabolismo
Centrômero/metabolismo
Fosforilação
Proteína Fosfatase 2/metabolismo
Proteólise
Separase/metabolismo
Fuso Acromático/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (Chromosomal Proteins, Non-Histone); 0 (Saccharomyces cerevisiae Proteins); 0 (cohesins); EC 2.7.11.1 (Casein Kinase I); EC 2.7.11.1 (HRR25 protein, S cerevisiae); EC 3.1.3.16 (Protein Phosphatase 2); EC 3.4.22.49 (Separase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161227
[St] Status:MEDLINE



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