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https://www.readbyqxmd.com/read/29348145/fbxl13-directs-the-proteolysis-of-cep192-to-regulate-centrosome-homeostasis-and-cell-migration
#1
Ella Fung, Carmen Richter, Hong-Bin Yang, Isabell Schäffer, Roman Fischer, Benedikt M Kessler, Florian Bassermann, Vincenzo D'Angiolella
Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192...
January 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29346133/dexmedetomidine-impairs-diaphragm-function-and-increases-oxidative-stress-but-does-not-aggravate-diaphragmatic-atrophy-in-mechanically-ventilated-rats
#2
Thomas Breuer, Christian Bleilevens, Rolf Rossaint, Gernot Marx, Julian Gehrenkemper, Henning Dierksen, Antoine Delpierre, Joachim Weis, Ghislaine Gayan-Ramirez, Christian S Bruells
BACKGROUND: Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients' mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction. METHODS: Twenty-four rats were separated into three groups (n = 8/group)...
January 18, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29343641/degradation-of-fbxo31-by-apc-c-is-regulated-by-akt-and-atm-mediated-phosphorylation
#3
Srinadh Choppara, Sunil K Malonia, Ganga Sankaran, Michael R Green, Manas Kumar Santra
The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31 levels are normally low but increase substantially following genotoxic stress through a mechanism that remains to be determined...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343579/identification-of-poxvirus-genome-uncoating-and-dna-replication-factors-with-mutually-redundant-roles
#4
Baoming Liu, Debasis Panda, Jorge D Mendez-Rios, Sundar Ganesan, Linda S Wyatt, Bernard Moss
Genome uncoating is essential for replication of most viruses. For poxviruses, the process is divided into two stages: removal of the envelope allowing early gene expression, and breaching of the core wall allowing DNA release, replication and late gene expression. Subsequent studies showed that the host proteasome and the viral D5 protein, which has an essential role in DNA replication, are required for vaccinia virus (VACV) genome uncoating. In a search for additional VACV uncoating proteins, we noted a report that described a defect in DNA replication and late expression when the gene encoding a 68 kDa ankyrin-repeat/F box protein (68k-ank), associated with the cellular SCF ubiquitin ligase complex, was deleted from the attenuated modified vaccinia virus Ankara (MVA)...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29330894/structure-function-and-evolution-of-the-hemerythrin-like-domain-superfamily
#5
Claudia Alvarez-Carreño, Vikram Alva, Arturo Becerra, Antonio Lazcano
Hemerythrin-like proteins have generally been studied for their ability to reversibly bind oxygen through their binuclear non-heme iron centers. However, in recent years, it has become increasingly evident that some members of the hemerythrin-like superfamily also participate in many other biological processes. For instance, the binuclear non-heme iron site of YtfE, a hemerythrin-like protein involved in the repair of iron centers in Escherichia coli, catalyzes the reduction of nitric oxide to nitrous oxide, and the human F-box/LRR-repeat protein 5, which contains a hemerythrin-like domain, is involved in intracellular iron homeostasis...
January 13, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29317510/the-f-box-protein-fbp1-shapes-the-immunogenic-potential-of-cryptococcus-neoformans
#6
Jorge Masso-Silva, Vanessa Espinosa, Tong-Bao Liu, Yina Wang, Chaoyang Xue, Amariliz Rivera
Cryptococcus neoformans is the main etiologic agent of cryptococcal meningitis and causes a significant number of deadly infections per year. Although it is well appreciated that host immune responses are crucial for defense against cryptococcosis, our understanding of factors that control the development of effective immunity to this fungus remains incomplete. In previous studies, we identified the F-box protein Fbp1 as a novel determinant of C. neoformans virulence. In this study, we found that the hypovirulence of the fbp1Δ mutant is linked to the development of a robust host immune response...
January 9, 2018: MBio
https://www.readbyqxmd.com/read/29310837/assessment-of-a-fbxw8-frameshift-mutation-c-1312_1313delgt-in-breast-cancer-patients-and-controls-from-central-europe
#7
Jing Wang, Natalia Bogdanova, Peter Schürmann, Tjoung-Won Park-Simon, Robert Geffers, Thilo Dörk
F-box proteins participate in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins, such as cyclin D1 as target of FBXW8. To investigate the spectrum of FBXW8 germ-line mutations in patients with breast cancer and healthy controls, we analyzed the whole FBXW8 coding region and flanking untranslated portions in germ-line DNA samples of 91 breast cancer patients and 277 healthy controls using next-generation amplicon sequencing. Five missense variants, one splice site variant, one frameshift variant, one synonymous variant, and one variant in the 3'-UTR were identified...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29300929/downregulation-of-skp2-in-papillary-thyroid-cancer-acts-synergistically-with-trail-on-inducing-apoptosis-via-ros
#8
Poyil Pratheeshkumar, Abdul K Siraj, Sasidharan Padmaja Divya, Sandeep Kumar Parvathareddy, Rafia Begum, Roxanne Melosantos, Saif S Al-Sobhi, Mohammed Al-Dawish, Fouad Al-Dayel, Khawla S Al-Kuraya
Context and Objective: S-phase kinase protein 2 (SKP2), is an F-box protein with proteasomal properties and has been found to be overexpressed in a variety of cancers. However, its role in papillary thyroid cancer (PTC) has not been fully elucidated. Experimental Design: SKP2 expression was assessed by immunohistochemistry in a tissue microarray format on a cohort of more than 1000 PTC samples. In vitro and in vivo studies were performed using proteasome inhibitor bortezomib and proapoptopic death ligand TRAIL either alone or combination on PTC cell lines...
December 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29299176/f-box-proteins-in-epigenetic-regulation-of-cancer
#9
REVIEW
Jia Shen, Charles Spruck
Epigenetic abnormalities are now realized as important as genetic alterations in contributing to the initiation and progression of cancer. Recent advancements in the cancer epigenetics field have identified extensive alterations of the epigenetic network in human cancers, including histone modifications and DNA methylation. F-box proteins, the substrate receptors of SCF (SKP1-Cullin1-F-box protein) E3 ubiquitin ligases, can directly and indirectly affect the balance of epigenetic regulation. In this brief review, we discuss our current understanding of F-box proteins in cellular epigenetic regulation and how dysregulation of these processes contribute to cancer development...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295941/the-osfbk1-e3-ligase-subunit-affects-anther-and-root-secondary-cell-wall-thickenings-by-mediating-turn-over-of-a-cinnamoyl-coa-reductase
#10
Pratikshya Borah, Jitendra P Khurana
Regulated proteolysis by the Ubiquitin-26S proteasome system challenges transcription and phosphorylation in magnitude and is one of the most important regulatory mechanisms in plants. This article describes the characterization of a rice auxin-responsive Kelch-domain containing F-box protein, OsFBK1, found to be a component of an SCF E3 ligase by interaction studies in yeast. Rice transgenics of OsFBK1 displayed variations in anther and root secondary cell wall content; it could be corroborated by electron/confocal microscopy and lignification studies, with no apparent changes in auxin content/signalling pathway...
January 2, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29284022/a-transcriptomics-approach-uncovers-novel-roles-for-poly-adp-ribosyl-ation-in-the-basal-defense-response-in-arabidopsis-thaliana
#11
Amy G Briggs, Lori C Adams-Phillips, Brian D Keppler, Sophia G Zebell, Kyle C Arend, April A Apfelbaum, Joshua A Smith, Andrew F Bent
Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) or loss of Arabidopsis thaliana PARG1 (poly(ADP-ribose) glycohydrolase) disrupt a subset of plant defenses. In the present study we examined the impact of altered poly(ADP-ribosyl)ation on early gene expression induced by the microbe-associate molecular patterns (MAMPs) flagellin (flg22) and EF-Tu (elf18). Stringent statistical analyses and filtering identified 178 genes having MAMP-induced mRNA abundance patterns that were altered by either PARP inhibitor 3-aminobenzamide (3AB) or PARG1 knockout...
2017: PloS One
https://www.readbyqxmd.com/read/29279382/structural-basis-of-the-phosphorylation-independent-recognition-of-cyclin-d1-by-the-scffbxo31-ubiquitin-ligase
#12
Yunfeng Li, Kai Jin, Eric Bunker, Xiaojuan Zhang, Xuemei Luo, Xuedong Liu, Bing Hao
Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCFFBXO31 (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29278851/f-box-protein-11-promotes-the-growth-and-metastasis-of-gastric-cancer-via-pi3k-akt-pathway-mediated-emt
#13
Caixia Sun, Youmao Tao, Yongjian Gao, Yufeng Xia, Ying Liu, Gang Wang, Ye Gu
F-box protein 11 (FBXO11) has both the E3 ubiquitin ligase activity and the methyltrasferase activity, and regulates metastasis, apoptosis and chemosensitivity in human cancer. However, the clinical significance and biological function of FBXO11 in gastric cancer (GC) are rarely known. Here, we demonstrated up-regulated expression of FBXO11 in GC tissues in comparison with that in tumor-adjacent tissues. Clinical analysis based on our specimens and the TCGA database revealed that FBXO11 overexpression was associated with large tumor size, lymph node metastasis and advanced TNM stage...
December 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29273730/the-f-box-protein-fkf1-inhibits-dimerization-of-cop1-in-the-control-of-photoperiodic-flowering
#14
Byoung-Doo Lee, Mi Ri Kim, Min-Young Kang, Joon-Yung Cha, Su-Hyun Han, Ganesh M Nawkar, Yasuhito Sakuraba, Sang Yeol Lee, Takato Imaizumi, C Robertson McClung, Woe-Yeon Kim, Nam-Chon Paek
In Arabidopsis thaliana, CONSTANS (CO) plays an essential role in the regulation of photoperiodic flowering under long-day conditions. CO protein is stable only in the afternoon of long days, when it induces the expression of FLOWERING LOCUS T (FT), which promotes flowering. The blue-light photoreceptor FLAVIN-BINDING, KELCH REPEAT, F-BOX1 (FKF1) interacts with CO and stabilizes it by an unknown mechanism. Here, we provide genetic and biochemical evidence that FKF1 inhibits CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1)-dependent CO degradation...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29251491/glycosylation-promotes-random-coil-to-helix-transition-in-a-region-of-a-protist-skp1-associated-with-f-box-binding
#15
Xianzhong Xu, Alexander Eletsky, M Osman Sheikh, James H Prestegard, Christopher M West
Cullin-Ring-Ligases mediate protein polyubiquitination, a signal for degradation in the 26S-proteasome. The CRL1 class consists of Skp1/cullin-1/F-box protein/Rbx1 (SCF) complexes that cyclically associate with ubiquitin-E2 to build the polyubiquitin chain. Within the SCF complex, the 162-amino acid DdSkp1 from Dictyostelium bridges cullin-1 with an F-box protein (FBP), the specificity factor for substrate selection. The hydroxylation-dependent glycosylation of Pro143 of DdSkp1 by a pentasaccharide forms the basis of a novel O2-sensing mechanism in the social amoeba Dictyostelium and other protists...
December 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/29244865/the-arabidopsis-thaliana-f-box-gene-hawaiian-skirt-is-a-new-player-in-the-microrna-pathway
#16
Xuebin Zhang, Dasuni Jayaweera, Janny L Peters, Judit Szecsi, Mohammed Bendahmane, Jeremy A Roberts, Zinnia H González-Carranza
In Arabidopsis, the F-box HAWAIIAN SKIRT (HWS) protein is important for organ growth. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion. To dissect the HWS role, we EMS-mutagenized hws-1 seeds and screened for mutations that suppress hws-1 associated phenotypes. We identified shs-2 and shs-3 (suppressor of hws-2 and 3) mutants in which the sepal fusion phenotype of hws-1 was suppressed. shs-2 and shs-3 (renamed hst-23/hws-1 and hst-24/hws-1) carry transition mutations that result in premature terminations in the plant homolog of Exportin-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport...
2017: PloS One
https://www.readbyqxmd.com/read/29236054/genome-wide-profiling-of-small-rnas-and-degradome-revealed-conserved-regulations-of-mirnas-on-auxin-responsive-genes-during-fruit-enlargement-in-peaches
#17
Mengya Shi, Xiao Hu, Yu Wei, Xu Hou, Xue Yuan, Jun Liu, Yueping Liu
Auxin has long been known as a critical phytohormone that regulates fruit development in plants. However, due to the lack of an enlarged ovary wall in the model plants Arabidopsis and rice, the molecular regulatory mechanisms of fruit division and enlargement remain unclear. In this study, we performed small RNA sequencing and degradome sequencing analyses to systematically explore post-transcriptional regulation in the mesocarp at the hard core stage following treatment of the peach (Prunus persica L.) fruit with the synthetic auxin α-naphthylacetic acid (NAA)...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29228602/fbxw8-dependent-degradation-of-mrfap1-in-anaphase-controls-mitotic-cell-death
#18
Duan-Zhuo Li, Shun-Fang Liu, Lan Zhu, Yu-Xing Wang, Yi-Xiang Chen, Jie Liu, Gang Hu, Xin Yu, Jian Li, Jin Zhang, Zhi-Xiang Wu, Han Lu, Wei Liu, Bin Liu
Mof4 family associated protein 1 (MRFAP1) is a 14 kDa nuclear protein, which involves in maintaining normal histone modification levels by negatively regulating recruitment of the NuA4 (nucleosome acetyltransferase of H4) histone acetyltransferase complex to chromatin. MRFAP1 has been identified as one of the most up-regulated proteins after NEDD8 (neural precursor cell expressed developmentally down-regulated 8) inhibition in multiple human cell lines. However, the biological function of MRFAP1 and the E3 ligase that targets MRFAP1 for destruction remain mysterious...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225355/evolutionary-conservation-and-functional-divergence-of-the-lfk-gene-family-play-important-roles-in-the-photoperiodic-flowering-pathway-of-land-plants
#19
Ling Lu, Yuanqi Wu, Zhengqiao Liao, Jing Xiong, Fengkai Wu, Jie Xu, Hai Lan, Qiling Tang, Shufeng Zhou, Yaxi Liu, Yanli Lu
ZEITLUPE (ZTL), LOV KELCH PROTEIN 2 (LKP2), and FLAVIN-BINDING KELCH REPEAT F-BOX 1 (FKF1)-blue-light photoreceptors-play important roles in regulating the circadian clock and photoperiodic flowering pathway in plants. In this study, phylogenetic analysis revealed that the LOV (Light, Oxygen, or Voltage) and Kelch repeat-containing F-box (LFK) gene family can be classified into two clades, ZTL/LKP2 and FKF1, with clear differentiation between monocots and dicots within each clade. The LFK family genes underwent strong purifying selection; however, signatures of positive selection to adapt to local conditions still existed in 18 specific codons...
December 11, 2017: Heredity
https://www.readbyqxmd.com/read/29212814/structural-basis-for-assembly-of-the-cbf3-kinetochore-complex
#20
Vera Leber, Andrea Nans, Martin R Singleton
Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP-A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP-ACse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single-particle cryo-EM reconstruction of the core CBF3 complex, incorporating the sequence-specific DNA-binding protein Cep3 together with regulatory subunits Ctf13 and Skp1...
December 6, 2017: EMBO Journal
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