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https://www.readbyqxmd.com/read/28319092/the-tdh-gcn5l1-fbxo15-kbp-axis-limits-mitochondrial-biogenesis-in-mouse-embryonic-stem%C3%A2-cells
#1
Valerio Donato, Massimo Bonora, Daniele Simoneschi, Davide Sartini, Yasusei Kudo, Anita Saraf, Laurence Florens, Michael P Washburn, Matthias Stadtfeld, Paolo Pinton, Michele Pagano
Self-renewing naive mouse embryonic stem cells (mESCs) contain few mitochondria, which increase in number and volume at the onset of differentiation. KBP (encoded by Kif1bp) is an interactor of the mitochondrial-associated kinesin Kif1Bα. We found that TDH, responsible for mitochondrial production of acetyl-CoA in mESCs, and the acetyltransferase GCN5L1 cooperate to acetylate Lys501 in KBP, allowing its recognition by and degradation via Fbxo15, an F-box protein transcriptionally controlled by the pluripotency core factors and repressed following differentiation...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28298444/scffbxo17-e3-ligase-modulates-inflammation-by-regulating-proteasomal-degradation-of-glycogen-synthase-kinase-3%C3%AE-in-lung-epithelia
#2
Tomeka Suber, Jianxin Wei, Anastasia M Jacko, Ina Nikolli, Yutong Zhao, Jing Zhao, Rama K Mallampalli
Glycogen synthase kinase-3β (GSK3β) has diverse biological roles including effects on cellular differentiation, migration, and inflammation. GSK3β phosphorylates proteins to generate phosphodegrons necessary for recognition by Skip-1/Cullin-1/F-box (SCF) E3 ubiquitin ligases leading to subsequent proteasomal degradation of these substrates. However, little is known regarding how GSK3β protein stability itself is regulated and how its stability may influence inflammation. Here we show that GSK3β is degraded by the ubiquitin-proteasome pathway in murine lung epithelial (MLE) cells through lysine 183 as an acceptor site for K48 polyubiquitination...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28296622/a-cell-based-screening-approach-for-identifying-protein-degradation-regulators
#3
Scott Simanski, Marie E Maloof, Trey K Sato, Valerie Cavett, Jennifer Caldwell Busby, Nagi G Ayad
Cellular transitions are achieved by the concerted actions of regulated degradation pathways. In the case of the cell cycle, ubiquitin mediated degradation ensures unidirectional transition from one phase to another. For instance, turnover of the cell cycle regulator cyclin B1 occurs after metaphase to induce mitotic exit. To better understand pathways controlling cyclin B1 turnover, the N terminal domain of cyclin B1 was fused to luciferase to generate an N-cyclin B1-luciferase protein that can be used as a reporter for protein turnover...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28294417/progressive-resistance-loaded-voluntary-wheel-running-increases-hypertrophy-and-differentially-affects-muscle-protein-synthesis-ribosome-biogenesis-and-proteolytic-markers-in-rat-muscle
#4
C B Mobley, A M Holland, W C Kephart, P W Mumford, R P Lowery, A N Kavazis, J M Wilson, M D Roberts
We examined if 6 weeks of progressive resistance-loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational efficiency, ribosome biogenesis, and markers of proteolysis. For 6 weeks, 8 male Sprague-Dawley rats (~9-10 weeks of age, ~300-325 g) rats were assigned to the progressive resistance-loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel-loading paradigm was as follows - days 1-7: free-wheel resistance, days 8-15: wheel resistance set to 20%-25% body mass, days 16-24: 40% body mass, days 25-32: 60% body mass, days 33-42: 40% body mass...
March 15, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28281075/concentration-dependent-alterations-in-gene-expression-induced-by-cadmium-in-solanum-lycopersicum
#5
Jing Hou, Xinhui Liu, Baoshan Cui, Junhong Bai, Xiangke Wang
Cadmium (Cd) toxicity in agricultural soil has received significant attention because of its higher transformation in the food chain and toxicity to humans. The aim of the present study was to develop sensitive and specific biomarkers for Cd stress. Therefore, transcriptional analyses were performed to investigate concentration-response characteristics of Cd responsive genes identified from a Solanum lycopersicum microarray. The results showed that the lowest observable adverse effect concentrations (LOAECs) of Cd to S...
March 10, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28242758/cdk5-fbw7-dependent-ubiquitination-and-degradation-of-ezh2-inhibits-pancreatic-cancer-cell-migration-and-invasion
#6
Xin Jin, Chong Yang, Ping Fan, Jun Xiao, Wanli Zhang, Sudong Zhan, Tao Liu, Dejie Wang, Heshui Wu
Pancreatic cancer is one of the most lethal cancer types. Enhancer of zeste homolog 2 (EZH2) is an oncogenic protein and overexpressed in pancreatic cancer, and EZH2 could be a potential therapeutic target for the treatment of pancreatic cancer. Although significant progress has been made toward understanding the function and deregulation of EZH2 in cancer cells, the post-translational regulation of EZH2 in cancer cells is still unclear. F-box and WD repeat domain-containing 7 (FBW7) acts as a tumor suppressor by targeting multiple oncoprotein substrates for ubiquitination and degradation...
February 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28236275/gene-expression-profiles-predictive-of-cold-induced-sweetening-in-potato
#7
Jonathan Neilson, M Lagüe, S Thomson, F Aurousseau, A M Murphy, B Bizimungu, V Deveaux, Y Bègue, J M E Jacobs, H H Tai
Cold storage (2-4 °C) used in potato production to suppress diseases and sprouting during storage can result in cold-induced sweetening (CIS), where reducing sugars accumulate in tuber tissue leading to undesirable browning, production of bitter flavors, and increased levels of acrylamide with frying. Potato exhibits genetic and environmental variation in resistance to CIS. The current study profiles gene expression in post-harvest tubers before cold storage using transcriptome sequencing and identifies genes whose expression is predictive for CIS...
February 24, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#8
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28216227/nek7-protects-telomeres-from-oxidative-dna-damage-by-phosphorylation-and-stabilization-of-trf1
#9
Rong Tan, Satoshi Nakajima, Qun Wang, Hongxiang Sun, Jing Xue, Jian Wu, Sabine Hellwig, Xuemei Zeng, Nathan A Yates, Thomas E Smithgall, Ming Lei, Yu Jiang, Arthur S Levine, Bing Su, Li Lan
Telomeric repeat binding factor 1 (TRF1) is essential to the maintenance of telomere chromatin structure and integrity. However, how telomere integrity is maintained, especially in response to damage, remains poorly understood. Here, we identify Nek7, a member of the Never in Mitosis Gene A (NIMA) kinase family, as a regulator of telomere integrity. Nek7 is recruited to telomeres and stabilizes TRF1 at telomeres after damage in an ATM activation-dependent manner. Nek7 deficiency leads to telomere aberrations, long-lasting γH2AX and 53BP1 foci, and augmented cell death upon oxidative telomeric DNA damage...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28209614/distinct-interactions-of-ebp1-isoforms-with-fbxw7-elicits-different-functions-in-cancer
#10
Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
The ErbB3 receptor binding protein EBP1 encodes two alternatively spliced isoforms p48 and p42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 p48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 p48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198417/chilling-affects-phytohormone-and-post-embryonic-development-pathways-during-bud-break-and-fruit-set-in-apple-malus-domestica-borkh
#11
Gulshan Kumar, Khushboo Gupta, Shivalika Pathania, Mohit Kumar Swarnkar, Usha Kumari Rattan, Gagandeep Singh, Ram Kumar Sharma, Anil Kumar Singh
The availability of sufficient chilling during bud dormancy plays an important role in the subsequent yield and quality of apple fruit, whereas, insufficient chilling availability negatively impacts the apple production. The transcriptome profiling during bud dormancy release and initial fruit set under low and high chill conditions was performed using RNA-seq. The comparative high number of differentially expressed genes during bud break and fruit set under high chill condition indicates that chilling availability was associated with transcriptional reorganization...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197531/targeting-sox9-for-degradation-to-inhibit-chemoresistance-metastatic-spread-and-recurrence
#12
Aldwin Suryo Rahmanto, Fredrik J Swartling, Olle Sangfelt
Cancer cells with stem-like properties are believed to contribute to treatment resistance, dissemination, and recurrence. SOX9 controls stem cell plasticity and its deregulation may provide a basis for tumor progression. Here, we summarize our findings of targeted SOX9 destruction by SCF(FBW7) (Skp1/Cul1/F-box) in medulloblastoma and its potential for therapeutic intervention.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28192820/estrogen-maintains-skeletal-muscle-in-septic-rats-associated-with-altering-hypothalamic-inflammation-and-neuropeptides
#13
Chenyan Zhao, Jun Li, Minhua Cheng, Jialing Shi, Juanhong Shen, Tao Gao, Fengchan Xi, Wenkui Yu
Muscle wasting is one of the main contributors to the worse outcomes in sepsis. Whether estrogen could alleviate muscle wasting induced by sepsis remains unclear. This study was designed to test the effect of estrogen on muscle wasting and its relationship with central alteration in sepsis. Thirty Sprague-Dawley rats were divided into 3 groups: control group, sepsis group, and estrogen treated sepsis group. Animals were intraperitoneally injected with lipopolysaccharide (10 mg/kg) or saline, followed by subcutaneous injection of 17β-estradiol (1 mg/kg) or saline...
February 13, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28184929/e3-ubiquitin-ligase-fbw7%C3%AE-inhibits-cholangiocarcinoma-cell-proliferation-by-downregulating-c-myc-and-cyclin-e
#14
Ming Li, Ling Ouyang, Zhigang Zheng, Dan Xiang, Aijun Ti, Leihua Li, Yuzhen Dan, Chundong Yu, Wengang Li
FBW7 (F-box and WD repeat domain-containing 7), also known as CDC4, AGO and SEL10, is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase. It is a recognized tumor suppressor because it targets multiple oncoproteins for ubiquitination-mediated destruction and its mutations are frequently identified in a variety of human malignancies. However, the function of FBW7 in proliferation of cholangiocarcinoma (CCA) remains unknown...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28184007/cyclin-f-fbxo1-interacts-with-hiv-1-vif-and-restricts-progeny-virion-infectivity-by-ubiquitination-and-proteasomal-degradation-of-vif-through-scf-cyclin-f-e3-ligase-machinery
#15
Tracy Augustine, Priyanka Chaudhary, Kailash Gupta, Sehbanul Islam, Payel Ghosh, Manas Kumar Santra, Debashis Mitra
Cyclin F, also known as FBXO1, is the largest among all cyclins which oscillates in the cell cycle like other cyclins. Apart from being a G2/M cyclin, Cyclin F functions as the substrate binding subunit of SCFCyclin F E3 ubiquitin ligase. In a gene expression analysis performed to identify novel gene modulations associated with cell cycle dysregulation during HIV-1 infection in CD4+ T cells, we observed down-regulation of Cyclin F (CCNF) gene. Later, using gene over expression and knockdown studies, we identified that Cyclin F negatively influences HIV-1 viral infectivity without any significant impact on virus production...
February 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28183327/characteristics-of-sirnas-derived-from-southern-rice-black-streaked-dwarf-virus-in-infected-rice-and-their-potential-role-in-host-gene-regulation
#16
Donglin Xu, Guohui Zhou
BACKGROUND: Virus-derived siRNAs (vsiRNAs)-mediated RNA silencing plays important roles in interaction between plant viruses and their hosts. Southern rice black-streaked dwarf virus (SRBSDV) is a newly emerged devastating rice reovirus with ten dsRNA genomic segments. The characteristics of SRBSDV-derived siRNAs and their biological implications in SRBSDV-rice interaction remain unexplored. METHODS: VsiRNAs profiling from SRBSDV-infected rice samples was done via small RNA deep sequencing...
February 10, 2017: Virology Journal
https://www.readbyqxmd.com/read/28139700/the-crystal-structure-of-the-sgt1-skp1-complex-the-link-between-hsp90-and-both-scf-e3-ubiquitin-ligases-and-kinetochores
#17
Oliver Willhoft, Richard Kerr, Dipali Patel, Wenjuan Zhang, Caezar Al-Jassar, Tina Daviter, Stefan H Millson, Konstantinos Thalassinos, Cara K Vaughan
The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways Sgt1 interacts with Skp1, a small protein that heterodimerizes with proteins containing the F-box motif. We have determined the crystal structure of the interacting domains of Saccharomyces cerevisiae Sgt1 and Skp1 at 2.8 Å resolution and validated the interface in the context of the full-length proteins in solution. The BTB/POZ domain of Skp1 associates with Sgt1 via the concave surface of its TPR domain using residues that are conserved in humans...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28117675/f-box-protein-fbxo22-mediates-polyubiquitination-and-degradation-of-cd147-to-reverse-cisplatin-resistance-of-tumor-cells
#18
Bo Wu, Zhen-Yu Liu, Jian Cui, Xiang-Min Yang, Lin Jing, Yang Zhou, Zhi-Nan Chen, Jian-Li Jiang
Drug resistance remains a major clinical obstacle to successful treatment of cancer. As posttranslational modification is becoming widely recognized to affect the function of oncoproteins, targeting specific posttranslational protein modification provides an attractive strategy for anticancer drug development. CD147 is a transmembrane glycoprotein contributing to chemo-resistance of cancer cells in a variety of human malignancies. Ubiquitination is an important posttranslational modification mediating protein degradation...
January 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28111017/structural-mimicry-by-a-bacterial-f-box-effector-hijacks-the-host-ubiquitin-proteasome-system
#19
Kathy Wong, John D Perpich, Guennadi Kozlov, Miroslaw Cygler, Yousef Abu Kwaik, Kalle Gehring
Ankyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K(48)-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains. Using X-ray crystallography, we determined the 3D structure of AnkB in complex with Skp1, a component of the human SCF ubiquitination ligase...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/28101194/inhibition-of-nedd8-and-fat10-ligase-activities-through-the-degrading-enzyme-nedd8-ultimate-buster-1-a-potential-anticancer-approach
#20
Ka-Liong Tan, Francesco Pezzella
The capabilities of tumour cells to survive through deregulated cell cycles and evade apoptosis are hallmarks of cancer. The ubiquitin-like proteins (UBL) proteasome system is important in regulating cell cycles via signaling proteins. Deregulation of the proteasomal system can lead to uncontrolled cell proliferation. The Skp, Cullin, F-box containing complex (SCF complex) is the predominant E3 ubiquitin ligase, and has diverse substrates. The ubiquitin ligase activity of the SCF complexes requires the conjugation of neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) to cullin proteins...
December 2016: Oncology Letters
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