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John F Dankert, Gergely Rona, Linda Clijsters, Phillip Geter, Jeffrey R Skaar, Keria Bermudez-Hernandez, Elizabeth Sassani, David Fenyö, Beatrix Ueberheide, Robert Schneider, Michele Pagano
SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A...
September 24, 2016: Molecular Cell
Chiung-Mei Chen, I-Cheng Chen, Ying-Lin Chen, Te-Hsien Lin, Wan-Ling Chen, Chih-Ying Chao, Yih-Ru Wu, Yeah-Ting Lu, Cheng-Yu Lee, Hong-Chi Chien, Ting-Shou Chen, Guey-Jen Lee-Chen, Chi-Mei Lee
BACKGROUND: The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. PURPOSE: We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP(+)-treated cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Shyam Ramachandran, Samantha R Osterhaus, Kalpaj R Parekh, Ashley M Jacobi, Mark A Behlke, Paul B McCray
We previously reported that delivery of a microRNA (miR)-138 mimic or siRNA against SIN3A to cultured cystic fibrosis (CF) (ΔF508/ΔF508) airway epithelia partially restored ΔF508-CFTR mediated cAMP-stimulated Cl-conductance. We hypothesized that dissecting this miR-138/SIN3A regulated gene network would identify individual proteins contributing to the rescue of ΔF508-CFTR function. Among the genes in the network, we rigorously validated candidates using functional CFTR maturation and electrolyte transport assays in polarized airway epithelia...
October 18, 2016: Journal of Biological Chemistry
Anne-Sophie Kratz, Kai T Richter, Yvonne T Schlosser, Miriam Schmitt, Anatoliy Shumilov, Henri-Jacques Delecluse, Ingrid Hoffmann
Topoisomerase IIα is an essential enzyme that resolves topological constraints in genomic DNA. It functions in disentangling intertwined chromosomes during anaphase leading to chromosome segregation thus preserving genomic stability. Here we describe a previously unrecognized mechanism regulating topoisomerase IIα activity that is dependent on the F-box protein Fbxo28. We find that Fbxo28, an evolutionarily conserved protein, is required for proper mitotic progression. Interfering with Fbxo28 function leads to a delay in metaphase-to-anaphase progression resulting in mitotic defects as lagging chromosomes, multipolar spindles and multinucleation...
October 18, 2016: Cell Cycle
Yuya Yamagishi, Marc Tessier-Lavigne
Axon degeneration is a tightly regulated, self-destructive program that is a critical feature of many neurodegenerative diseases, but the molecular mechanisms regulating this program remain poorly understood. Here, we identify S-phase kinase-associated protein 1A (Skp1a), a core component of a Skp/Cullin/F-box (SCF)-type E3 ubiquitin ligase complex, as a critical regulator of axon degeneration after injury in mammalian neurons. Depletion of Skp1a prolongs survival of injured axons in vitro and in the optic nerve in vivo...
October 11, 2016: Cell Reports
Jahanshah Ashkani, D J G Rees
Specificity in the GSI response results from the S-haplotype-specific molecular interaction of S-locus F-box (SLF/SFB) and SRNase proteins in the self-incompatibility locus (S-locus). The answer to the question of how these two components of the S-locus (SRNase and SLF/SFB) interact has been gathered from several models. Since there is not enough evidence as to which one is the definitive model, none of them can be ruled out. Despite the identification of interacting protein elements, the mechanism by which SLF/SFB and SRNase interact to differently trigger the self-incompatibility among families and subfamilies remain uncertain...
October 10, 2016: Scientific Reports
Shifeng Su, Xiaoyu Chen, Jiang Geng, John T Minges, Gail Grossman, Elizabeth M Wilson
Melanoma antigen-A11 (MAGE-A11) is a proto-oncogene involved in androgen receptor signaling and androgen-dependent cell growth. In this report we provide evidence that MAGE-A11 interacts with Skp2 (S phase kinase-associated protein), the substrate recognition protein of the Skp1-Cullin1-F-box E3 ubiquitin ligase, and with Skp2 binding protein, cyclin A. A similar cyclin A binding motif in MAGE-A11 and Skp2A was consistent with a competitive relationship between MAGE-A11 and Skp2 in binding cyclin A. Skp2 inhibited MAGE-A11 interaction with cyclin A...
October 6, 2016: Molecular and Cellular Endocrinology
Karolina Stefanowicz, Nausicaä Lannoo, Yafei Zhao, Lore Eggermont, Jonas Van Hove, Bassam Al Atalah, Els J M Van Damme
BACKGROUND: A small group of F-box proteins consisting of a conserved F-box domain linked to a domain homologous to the glycan-binding protein has been identified within the genome of Arabidopsis thaliana. Previously, the so-called F-box-Nictaba protein, encoded by the gene At2g02360, was shown to be a functional lectin which binds N-acetyllactosamine structures. Here, we present a detailed qRT-PCR expression analysis of F-box-Nictaba in Arabidopsis plants upon different stresses and hormone treatments...
October 4, 2016: BMC Plant Biology
Yan Ma, Meijuan Yan, Hua Huang, Li Zhang, Qian Wang, Yaqi Zhao, Jianmei Zhao
Non-Hodgkin lymphoma (NHL) is a primary tumor arising in lymph nodes and lymphoid tissue. The incidence of NHL is increasing at an annual rate of 3%. The human Jun activation domain-binding protein 1/COP9 signalosome subunit 5 (Jab1/CSN5) is a negative regulator of the cell cycle inhibitor p27(Kip1) and abnormal expression of Jab1 is correlated with reduced p27 expression and associated with advanced tumor stage and poor prognosis in several human cancers. F-box protein S-phase kinase-interacting protein-2 (Skp2), the substrate recognition subunit of the Skp1-Cul1-F-box protein ubiquitin protein ligase complex, is required for the ubiquitination and consequent degradation of p27...
October 2016: Molecular and Clinical Oncology
Zhan Zhao, Yadong Xue, Huili Yang, Huimin Li, Gaoyang Sun, Xiaofeng Zhao, Dong Ding, Jihua Tang
Internode length is one of the decisive factors affecting plant height (PH) and ear height (EH), which are closely associated with the lodging resistance, biomass and grain yield of maize. miRNAs, currently recognized as important transcriptional/ post-transcriptional regulators, play an essential role in plant growth and development. However, their roles in developing internodes under maize ears remain unclear. To identify the roles of miRNAs and their targets in the development of internodes under maize ears, six miRNA and two degradome libraries were constructed using the 7th, 8th and 9th internodes of two inbred lines, 'Xun928' and 'Xun9058', which had significantly different internode lengths...
2016: PloS One
Marta Delgado-Camprubi, Noemi Esteras, Marc Pm Soutar, Helene Plun-Favreau, Andrey Y Abramov
The Parkinson's disease (PD)-related protein F-box only protein 7 (Fbxo7) is the substrate-recognition component of the Skp1-Cullin-F-box protein E3 ubiquitin ligase complex. We have recently shown that PD-associated mutations in Fbxo7 disrupt mitochondrial autophagy (mitophagy), suggesting a role for Fbxo7 in modulating mitochondrial homeostasis. Here we report that Fbxo7 deficiency is associated with reduced cellular NAD(+) levels, which results in increased mitochondrial NADH redox index and impaired activity of complex I in the electron transport chain...
September 30, 2016: Cell Death and Differentiation
Bastian Jöhnk, Özgür Bayram, Anja Abelmann, Thorsten Heinekamp, Derek J Mattern, Axel A Brakhage, Ilse D Jacobsen, Oliver Valerius, Gerhard H Braus
F-box proteins share the F-box domain to connect substrates of E3 SCF ubiquitin RING ligases through the adaptor Skp1/A to Cul1/A scaffolds. F-box protein Fbx15 is part of the general stress response of the human pathogenic mold Aspergillus fumigatus. Oxidative stress induces a transient peak of fbx15 expression, resulting in 3x elevated Fbx15 protein levels. During non-stress conditions Fbx15 is phosphorylated and F-box mediated interaction with SkpA preferentially happens in smaller subpopulations in the cytoplasm...
September 2016: PLoS Pathogens
Aldwin Suryo Rahmanto, Vasil Savov, Andrä Brunner, Sara Bolin, Holger Weishaupt, Alena Malyukova, Gabriela Rosén, Matko Čančer, Sonja Hutter, Anders Sundström, Daisuke Kawauchi, David Tw Jones, Charles Spruck, Michael D Taylor, Yoon-Jae Cho, Stefan M Pfister, Marcel Kool, Andrey Korshunov, Fredrik J Swartling, Olle Sangfelt
SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here, we show that SOX9 is a substrate of FBW7, a tumor suppressor, and a SCF (SKP1/CUL1/F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase and consequently degraded by SCF(FBW) (7α) Failure to degrade SOX9 promotes migration, metastasis, and treatment resistance in medulloblastoma, one of the most common childhood brain tumors...
September 13, 2016: EMBO Journal
Lian Jin, Qingqing Qin, Yu Wang, Yingying Pu, Lifang Liu, Xing Wen, Shaoyi Ji, Jianguo Wu, Chunhong Wei, Biao Ding, Yi Li
The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes. Microbe infection can disturb auxin signaling resulting in defects in these processes, but the underlying mechanisms are poorly understood. Auxin signaling begins with perception of auxin by a transient co-receptor complex consisting of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB) protein and an auxin/indole-3-acetic acid (Aux/IAA) protein. Auxin binding to the co-receptor triggers ubiquitination and 26S proteasome degradation of the Aux/IAA proteins, leading to subsequent events, including expression of auxin-responsive genes...
September 2016: PLoS Pathogens
Marek Marzec
Strigolactones (SLs), a recently discovered class of phytohormones, are important regulators of plant growth and development. While the biosynthetic pathway of these molecules is well documented, until recently there was not much known about the molecular mechanisms underlying SL perception and signal transduction in plants. Certain aspects of their perception and signaling, including the hormone-mediated interaction between receptor and F-box protein, degradation of suppressor proteins and activation of transcription factors, are also found in other phytohormones...
2016: Frontiers in Plant Science
Dayue Liu, Haoming Xia, Fang Wang, Cui Chen, Jianting Long
BACKGROUND: In this study, we investigated the functional correlation between microRNA-210 (miR-210) and gene of F-box protein 31 (FBXO31) in regulating breast cancer. METHODS: Dual-luciferase assay and quantitative real-time polymerase chain reaction were used to investigate the binding of miR-210 with FBXO31 and their expression patterns in breast cancer. miR-210 was inhibited in breast cancer T47D and MCF-7 cells to assess its effect on cancer proliferation, cell cycle progression, and migration...
2016: OncoTargets and Therapy
Gui-Yang Jiang, Xiu-Peng Zhang, Liang Wang, Xu-Yong Lin, Juan-Han Yu, En-Hua Wang, Yong Zhang
FBXO25 is a recently discovered protein that belongs to the Fbx class of the F-box family of proteins, and F-box proteins play a crucial role in tumorigenesis. However, the function of FBXO25 in cancer was not revealed so far. As measured by immunohistochemical staining, FBXO25 was highly expressed in the cytoplasm and nucleus of lung cancer samples (64.2 %, 136/212), compared with adjacent normal lung tissues (23.3 %, 7/30, p < 0.01). In addition, its expression was positively correlated with TNM staging (p < 0...
September 5, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Kyungshin Shin, Sang-Gu Hwang, Ik Joon Choi, Young-Gyu Ko, Jaemin Jeong, Heechung Kwon
Satellite cells attached to skeletal muscle fibers play a crucial role in skeletal muscle regeneration. During regeneration, the satellite cells proliferate, migrate to the damaged region, and fuse to each other. Although it is important to determine the cellular mechanisms controlling myoblast behavior, their regulators are not well understood. In this study, we evaluated the roles of Fbxw7 in primary myoblasts and determined its potential as a therapeutic target for muscle disease. We originally found that Fbxw7β, one of the E3 ubiquitin ligase Fbxw7 subtypes, negatively regulates differentiation, proliferation and migration of myoblasts and satellite cells on muscle fiber...
September 4, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
Benjamin Goeppert, Christina Ernst, Constance Baer, Stephanie Roessler, Marcus Renner, Arianeb Mehrabi, Mohammadreza Hafezi, Anita Pathil, Arne Warth, Albrecht Stenzinger, Wilko Weichert, Marion Bähr, Rainer Will, Peter Schirmacher, Christoph Plass, Dieter Weichenhan
Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs...
September 3, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Xiuying Wang, Yulan Liu, Shuhui Wang, Dingan Pi, Weibo Leng, Huiling Zhu, Jing Zhang, Haifeng Shi, Shuang Li, Xi Lin, Jack Odle
Pro-inflammatory cytokines are critical in mechanisms of muscle atrophy. In addition, asparagine (Asn) is necessary for protein synthesis in mammalian cells. We hypothesised that Asn could attenuate lipopolysaccharide (LPS)-induced muscle atrophy in a piglet model. Piglets were allotted to four treatments (non-challenged control, LPS-challenged control, LPS+0·5 % Asn and LPS+1·0 % Asn). On day 21, the piglets were injected with LPS or saline. At 4 h post injection, piglet blood and muscle samples were collected...
October 2016: British Journal of Nutrition
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