排序方式: 共有182条查询结果,搜索用时 15 毫秒
91.
Junpeng Yan Caili Hao Maria DeLucia Selene Swanson Laurence Florens Michael P. Washburn Jinwoo Ahn Jacek Skowronski 《The Journal of biological chemistry》2015,290(21):13279-13292
SAMHD1 is a nuclear deoxyribonucleoside triphosphate triphosphohydrolase that contributes to the control of cellular deoxyribonucleoside triphosphate (dNTP) pool sizes through dNTP hydrolysis and modulates the innate immune response to viruses. CyclinA2-CDK1/2 phosphorylates SAMHD1 at Thr-592, but how this modification controls SAMHD1 functions in proliferating cells is not known. Here, we show that SAMHD1 levels remain relatively unchanged during the cell division cycle in primary human T lymphocytes and in monocytic cell lines. Inactivation of the bipartite cyclinA2-CDK-binding site in the SAMHD1 C terminus described herein abolished SAMHD1 phosphorylation on Thr-592 during S and G2 phases thus interfering with DNA replication and progression of cells through S phase. The effects exerted by Thr-592 phosphorylation-defective SAMHD1 mutants were associated with activation of DNA damage checkpoint and depletion of dNTP concentrations to levels lower than those seen upon expression of wild type SAMHD1 protein. These disruptive effects were relieved by either mutation of the catalytic residues of the SAMHD1 phosphohydrolase domain or by a Thr-592 phosphomimetic mutation, thus linking the Thr-592 phosphorylation state to the control of SAMHD1 dNTPase activity. Our findings support a model in which phosphorylation of Thr-592 by cyclinA2-CDK down-modulates, but does not inactivate, SAMHD1 dNTPase in S phase, thereby fine-tuning SAMHD1 control of dNTP levels during DNA replication. 相似文献
92.
Selene M. Virk Richard M. Gibson Miguel E. Quinones-Mateu Jill S. Barnholtz-Sloan 《PloS one》2015,10(5)
Glioblastoma (GBM) is an aggressive, malignant brain tumor typically resulting in death of the patient within one year following diagnosis; and those who survive beyond this point usually present with tumor recurrence within two years (5-year survival is 5%). The genetic heterogeneity of GBM has made the molecular characterization of these tumors an area of great interest and has led to identification of molecular subtypes in GBM. The availability of sequencing platforms that are both fast and economical can further the adoption of tumor sequencing in the clinical environment, potentially leading to identification of clinically actionable genetic targets. In this pilot study, comprised of triplet samples of normal blood, primary tumor, and recurrent tumor samples from three patients; we compared the ability of Illumina whole exome sequencing (ExomeSeq) and the Ion AmpliSeq Comprehensive Cancer Panel (CCP) to identify somatic variants in patient-paired primary and recurrent tumor samples. Thirteen genes were found to harbor variants, the majority of which were exclusive to the ExomeSeq data. Surprisingly, only two variants were identified by both platforms and they were located within the PTCH1 and NF1 genes. Although preliminary in nature, this work highlights major differences in variant identification in data generated from the two platforms. Additional studies with larger samples sizes are needed to further explore the differences between these technologies and to enhance our understanding of the clinical utility of panel based platforms in genomic profiling of brain tumors. 相似文献
93.
Xiang Y Takeo S Florens L Hughes SE Huo LJ Gilliland WD Swanson SK Teeter K Schwartz JW Washburn MP Jaspersen SL Hawley RS 《PLoS biology》2007,5(12):e323
Many meiotic systems in female animals include a lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB). However, the mechanisms by which a meiotic cell can arrest for long periods of time (decades in human females) have remained a mystery. The Drosophila Matrimony (Mtrm) protein is expressed from the end of pachytene until the completion of meiosis I. Loss-of-function mtrm mutants result in precocious NEB. Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo kinase (Polo) in vivo, and multidimensional protein identification technology mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+ , demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm acts as a negative regulator of Polo during the later stages of G2 arrest. Indeed, both the repression of Polo expression until stage 11 and the inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles in maintaining and properly terminating G2 arrest. Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase. 相似文献
94.
Schneider J Wood A Lee JS Schuster R Dueker J Maguire C Swanson SK Florens L Washburn MP Shilatifard A 《Molecular cell》2005,19(6):849-856
The Set1-containing complex COMPASS, which is the yeast homolog of the human MLL complex, is required for mono-, di-, and trimethylation of lysine 4 of histone H3. We have performed a comparative global proteomic screen to better define the role of COMPASS in histone trimethylation. We report that both Cps60 and Cps40 components of COMPASS are required for proper histone H3 trimethylation, but not for proper regulation of telomere-associated gene silencing. Purified COMPASS lacking Cps60 can mono- and dimethylate but is not capable of trimethylating H3(K4). Chromatin immunoprecipitation (ChIP) studies indicate that the loss subunits of COMPASS required for histone trimethylation do not affect the localization of Set1 to chromatin for the genes tested. Collectively, our results suggest a molecular requirement for several components of COMPASS for proper histone H3 trimethylation and regulation of telomere-associated gene expression, indicating multiple roles for different forms of histone methylation by COMPASS. 相似文献
95.
The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex 下载免费PDF全文
Lee KK Florens L Swanson SK Washburn MP Workman JL 《Molecular and cellular biology》2005,25(3):1173-1182
Covalent modifications of the histone tails and the cross talk between these modifications are hallmark features of gene regulation. The SAGA histone acetyltransferase complex is one of the most well-characterized complexes involved in these covalent modifications. The recent finding that the removal of the ubiquitin group from H2B is performed by a component of SAGA, Ubp8, is intriguing as it assigns two posttranslation modification processes to one complex. In this work, we characterize the association of Ubp8 with SAGA and the effect that acetylation and deubiquitylation have on one another in vitro and in vivo. We found not only that Ubp8 is a part of the SAGA complex, but also that its deubiquitylation activity requires Ubp8's association with SAGA. Furthermore, we found that the Ubp8 association with SAGA requires Sgf11 and that this requirement is reciprocal. We also found that the acetylation and deubiquitylation activities of SAGA are independent of one another. However, we found that preacetylating histone H2B inhibited subsequent deubiquitylation. Additionally, we found that increasing the ubiquitylation state of H2B inhibited the expression of the ARG1 gene, whose repression was previously shown to require the RAD6 ubiquitin ligase. Taken together, these data indicate that the expression of some genes, including ARG1, is regulated by a balance of histone H2B ubiquitylation in the cell. 相似文献
96.
Shia WJ Osada S Florens L Swanson SK Washburn MP Workman JL 《The Journal of biological chemistry》2005,280(12):11987-11994
97.
Metal contaminations impact archaeal community composition,abundance and function in remote alpine lakes 下载免费PDF全文
Sergi Compte‐Port Carles M. Borrego Hélène Moussard Mathilde Jeanbille Claudia Ximena Restrepo‐Ortiz Alberto de Diego Azibar Rodriguez‐Iruretagoiena Ainara Gredilla Silvia Fdez‐Ortiz de Vallejuelo Pierre E. Galand Dimitri Kalenitchenko Jean‐Luc Rols Oleg S. Pokrovsky Aridane G. Gonzalez Lluis Camarero Selene Muñiz Enrique Navarro‐Navarro Jean‐Christophe Auguet 《Environmental microbiology》2018,20(7):2422-2437
98.
Jo?o Tavares Calixto Júnior Selene Maia de Morais Celeste Vega Gomez Cathia Coronel Molas Miriam Rolon Aline Augusti Boligon Margareth Linde Athayde Cícera Datiane de Morais Oliveira Saulo Relison Tintino Melo Coutinho Henrique Douglas 《Saudi Journal of Biological Sciences》2016,23(3):434-440
This work describes the antiparasitic and cytotoxic activities of three plant species from the Cerrado biome, Northeastern Brazil. Significant antiparasitic inhibition was observed against Trypanosoma cruzi (63.86%), Leishmania brasiliensis (92.20%) and Leishmania infantum (95.23%) when using ethanol extract from leaves of Guazuma ulmifolia Lam. (Malvaceae), at a concentration of 500 μg/mL. However, low levels of inhibition were observed when assessing leishmanicidal and trypanocidal (Clone CL-B5) activities of crude ethanol extracts from leaves and bast tissue of Luehea paniculata (Malvaceae) and leaves and bark of Prockia crucis (Salicaceae) at a concentration of 500 μg/mL. The extracts revealed the presence of phenolic acids such as gallic acid, chlorogenic acid, caffeic acid and rosmarinic acid, as well as flavonoids such as rutin, luteolin, apigenin and quercetin – the latter detected only in G. ulmifolia. G. ulmifolia extract displayed higher leishmanicidal activity probably due to the presence of quercetin, a potent known leishmanicidal compound. A cytotoxicity test indicated values over 50% at the highest concentration (1000 μg/mL) for all natural products, which were considered cytotoxic. This points out the need for further tests to enable future in vivo trials, including antineoplastic activity on human tumor cells. 相似文献
99.
100.
Jorge Alberto Achcar Selene Loibel 《Biometrical journal. Biometrische Zeitschrift》1998,40(5):543-555
Metropolis algorithms along with Gibbs steps are proposed to perform a Bayesian analysis for change-point constant hazard function models considering different prior densities for the parameters and censored survival data. We also present some generalizations for the comparison of two treatments. The methodology is illustrated with some examples. 相似文献