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https://www.readbyqxmd.com/read/29775578/c-terminal-end-directed-protein-elimination-by-crl2-ubiquitin-ligases
#1
Hsiu-Chuan Lin, Chi-Wei Yeh, Yen-Fu Chen, Ting-Ting Lee, Pei-Yun Hsieh, Domnita V Rusnac, Sung-Ya Lin, Stephen J Elledge, Ning Zheng, Hsueh-Chi S Yen
The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.e., C-end degrons). C-end degrons are mostly less than ten residues in length and comprise a few indispensable residues along with some rather degenerate ones...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29731868/microrna-192-5p-suppresses-the-initiation-and-progression-of-osteosarcoma-by-targeting-usp1
#2
Sheng Zhou, Min Xiong, Guo Dai, Ling Yu, Zhengpei Zhang, Jie Chen, Weichun Guo
Osteosarcoma is the most frequent primary malignant bone tumor. An increasing body of evidence has suggested that microRNAs (miRNA/miRs) have emerged as critical regulators in the initiation and progression of osteosarcoma. The present study explored the biological function of miR-192-5p and ubiquitin-specific protease 1 (USP1), and investigated whether miR-192-5p could directly interact with USP1 in osteosarcoma. The results revealed that miR-192-5p was significantly downregulated in osteosarcoma tissues and cell lines, while a reverse expression profile of USP1 was observed...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29138248/usp1-uaf1-deubiquitinase-complex-stabilizes-tbk1-and-enhances-antiviral-responses
#3
Zhongxia Yu, Hui Song, Mutian Jia, Jintao Zhang, Wenwen Wang, Qi Li, Lining Zhang, Wei Zhao
Optimal activation of TANK-binding kinase 1 (TBK1) is crucial for initiation of innate antiviral immunity and maintenance of immune homeostasis. Although several E3 ubiquitin ligases have been reported to regulate TBK1 activation by mediating its polyubiquitination, the functions of deubiquitinase on TBK1 activity remain largely unclear. Here, we identified a deubiquitinase complex, which is formed by ubiquitin specific peptidase 1 (USP1) and USP1-associated factor 1 (UAF1), as a viral infection-induced physiological enhancer of TBK1 expression...
December 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29091922/characterization-of-the-deubiquitination-activity-and-substrate-specificity-of-the-chicken-ubiquitin-specific-protease-1-usp-associated-factor-1-complex
#4
Hainan Zheng, Mengyun Wang, Chengcheng Zhao, Shanli Wu, Peifeng Yu, Yan Lü, Tiedong Wang, Yongxing Ai
Deubiquitinases (DUBs) are essential regulators of intracellular processes involving ubiquitin (Ub) modification. The human DUB ubiquitin-specific protease 1 (hUSP1) interacts with human USP-associated factor 1 (hUAF1), and helps to regulate processes such as DNA damage repair. Previously, we identified a chicken USP1 homologue (chUSP1) during an investigation into the properties of Marek's disease virus (MDV). However, chUSP1's deubiquitination activity, interaction with chUAF1, and substrate specificity remained unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28881649/identification-of-deubiquitinase-targets-of-isothiocyanates-using-silac-assisted-quantitative-mass-spectrometry
#5
Ann P Lawson, Daniel W Bak, D Alexander Shannon, Marcus J C Long, Tushara Vijaykumar, Runhan Yu, Farid El Oualid, Eranthie Weerapana, Lizbeth Hedstrom
Cruciferous vegetables such as broccoli and kale have well documented chemopreventative and anticancer effects that are attributed to the presence of isothiocyanates (ITCs). ITCs modulate the levels of many oncogenic proteins, but the molecular mechanisms of ITC action are not understood. We previously reported that phenethyl isothiocyanate (PEITC) inhibits two deubiquitinases (DUBs), USP9x and UCH37. DUBs regulate many cellular processes and DUB dysregulation is linked to the pathogenesis of human diseases including cancer, neurodegeneration, and inflammation...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28843894/modulation-of-gene-expression-by-nutritional-state-and-hormones-in-bombyx-larvae-in-relation-to-its-growth-period
#6
Bembem Thounaojam, Bela Keshan
Insect growth and development are mainly regulated via synchronization of many extrinsic and intrinsic factors such as nutrition and hormones. Previously we have demonstrated that larval growth period influences the effect of insulin on the accumulation of glycogen in the fat body of Bombyx larvae. In the present study we demonstrate that Bombyx larvae at the terminal growth period (TGP, after critical weight) had a significantly greater increase in the expression level of Akt in the fat body than at the active growth period (AGP, before critical weight)...
November 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28790182/protein-kinase-c-delta-phosphorylates-ecdysone-receptor-b1-to-promote-gene-expression-and-apoptosis-under-20-hydroxyecdysone-regulation
#7
Cai-Hua Chen, Jing Pan, Yu-Qin Di, Wen Liu, Li Hou, Jin-Xing Wang, Xiao-Fan Zhao
The nuclear receptor EcRB1, which is activated by the insect steroid hormone 20-hydroxyecdysone (20E), is reportedly phosphorylated by a protein kinase after 20E induction. However, the protein kinase has not been identified, and the significance of EcRB1 phosphorylation is unclear. In this study, we identified a protein kinase C δ (PKCδ) isoform (the E isoform) that phosphorylates EcRB1 in the lepidopteran Helicoverpa armigera , a serious agricultural pest worldwide, to promote apoptotic gene expression and apoptosis during metamorphosis...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28636932/ubiquitination-linked-phosphorylation-of-the-fanci-s-tq-cluster-contributes-to-activation-of-the-fanconi-anemia-i-d2-complex
#8
Ronald S Cheung, Maria Castella, Antonio Abeyta, Philip R Gafken, Nyka Tucker, Toshiyasu Taniguchi
Repair of interstrand crosslinks by the Fanconi anemia (FA) pathway requires both monoubiquitination and de-ubiquitination of the FANCI/FANCD2 (FANCI/D2) complex. In the standing model, the phosphorylation of six sites in the FANCI S/TQ cluster domain occurs upstream of, and promotes, FANCI/D2 monoubiquitination. We generated phospho-specific antibodies against three different S/TQ cluster sites (serines 556, 559, and 565) on human FANCI and found that, in contrast to the standing model, distinct FANCI sites were phosphorylated either predominantly upstream (ubiquitination independent; serine 556) or downstream (ubiquitination-linked; serines 559 and 565) of FANCI/D2 monoubiquitination...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28627638/meiotic-defects-and-decreased-expression-of-genes-located-around-the-chromosomal-breakpoint-in-the-testis-of-a-patient-with-a-novel-46-x-t-y-1-p11-3-p31-translocation
#9
Guangyuan Li, Furhan Iqbal, Liu Wang, Zhipeng Xu, Xiaoyan Che, Wen Yu, Liang Shi, Tonghang Guo, Guixiang Zhou, Xiaohua Jiang, Huan Zhang, Yuanwei Zhang, Dexin Yu
Balanced translocations are known to be associated with infertility, spontaneous abortions and birth defects in mammals. Spermatocyte spreading and immunostaining were applied to detect meiotic prophase I progression, homologous chromosome pairing, synapsis and recombination in an azoospermic reciprocal translocation 46,X,t(Y;1)(p11.3;p31) carrier. Histological examination of testicular sections revealed a severely reduced number of germ cells with no spermatids or sperm in the carrier. A significant reduction in XY recombination was observed in the patient...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28604711/the-anaphase-promoting-complex-impacts-repair-choice-by-protecting-ubiquitin-signalling-at-dna-damage-sites
#10
Kyungsoo Ha, Chengxian Ma, Han Lin, Lichun Tang, Zhusheng Lian, Fang Zhao, Ju-Mei Li, Bei Zhen, Huadong Pei, Suxia Han, Marcos Malumbres, Jianping Jin, Huan Chen, Yongxiang Zhao, Qing Zhu, Pumin Zhang
Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC(Cdh1) plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28472782/identification-of-deubiquitinase-targets-of-isothiocyanates-using-silac-assisted-quantitative-mass-spectrometry
#11
Ann P Lawson, Daniel W Bak, D Alexander Shannon, Marcus J C Long, Tushara Vijaykumar, Runhan Yu, Farid El Oualid, Eranthie Weerapana, Lizbeth Hedstrom
Cruciferous vegetables such as broccoli and kale have well documented chemopreventative and anticancer effects that are attributed to the presence of isothiocyanates (ITCs). ITCs modulate the levels of many oncogenic proteins, but the molecular mechanisms of ITC action are not understood. We previously reported that phenethyl isothiocyanate (PEITC) inhibits two deubiquitinases (DUBs), USP9x and UCH37. DUBs regulate many cellular processes and DUB dysregulation is linked to the pathogenesis of human diseases including cancer, neurodegeneration, and inflammation...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28302046/the-role-of-the-complex-usp1-wdr48-in-differentiation-and-proliferation-processes-in-cancer-stem-cells
#12
Jussara Maria Gonçalves, Mabel Mariela Rodriguez Cordeiro, Elena Riet Correa Rivero
Recently some studies identified the Basic-Helix-Loop-Helix (bHLH) transcription factor as a significant regulator for the evolution of neoplasms. The binding between bHLH proteins and DNA is restricted by heterodimerization with Inhibitors of DNA binding (ID). IDs prevent cellular differentiation, promote growth and sustain tumor development. The wide presence of stem cells in cancers suggests that genes ID are essential to cancer stem cells (CSC) progress. The enzyme Ubiquitin-specific protease 1 (USP1) is reported by deubiquitination and stabilization of IDs...
March 15, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28270494/blockade-of-deubiquitylating-enzyme-usp1-inhibits-dna-repair-and-triggers-apoptosis-in-multiple-myeloma-cells
#13
Deepika Sharma Das, Abhishek Das, Arghya Ray, Yan Song, Mehmet Kemal Samur, Nikhil C Munshi, Dharminder Chauhan, Kenneth C Anderson
Purpose: The ubiquitin proteasome pathway is a validated therapeutic target in multiple myeloma. Deubiquitylating enzyme USP1 participates in DNA damage response and cellular differentiation pathways. To date, the role of USP1 in multiple myeloma biology is not defined. In the present study, we investigated the functional significance of USP1 in multiple myeloma using genetic and biochemical approaches. Experimental Design: To investigate the role of USP1 in myeloma, we utilized USP1 inhibitor SJB3-019A (SJB) for studies in myeloma cell lines and patient multiple myeloma cells...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28011342/understanding-and-predicting-the-impact-of-critical-dissolution-variables-for-nifedipine-immediate-release-capsules-by-multivariate-data-analysis
#14
A Mercuri, M Pagliari, F Baxevanis, R Fares, N Fotaki
In this study the selection of in vivo predictive in vitro dissolution experimental set-ups using a multivariate analysis approach, in line with the Quality by Design (QbD) principles, is explored. The dissolution variables selected using a design of experiments (DoE) were the dissolution apparatus [USP1 apparatus (basket) and USP2 apparatus (paddle)], the rotational speed of the basket/or paddle, the operator conditions (dissolution apparatus brand and operator), the volume, the pH, and the ethanol content of the dissolution medium...
February 25, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27986371/mechanism-of-ubiquitination-and-deubiquitination-in-the-fanconi-anemia-pathway
#15
Sylvie van Twest, Vincent J Murphy, Charlotte Hodson, Winnie Tan, Paolo Swuec, Julienne J O'Rourke, Jörg Heierhorst, Wayne Crismani, Andrew J Deans
Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The "FA core complex" contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by FANCB and FAAP100...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/27756680/steady-state-kinetic-studies-reveal-that-the-anti-cancer-target-ubiquitin-specific-protease-17-usp17-is-a-highly-efficient-deubiquitinating-enzyme
#16
Nicole M Hjortland, Andrew D Mesecar
USP17 is a deubiquitinating enzyme that is upregulated in numerous cancers and therefore a drug target. We developed a robust expression, purification, and assay system for USP17 enabling its enzymatic and structural characterization. USP17 was expressed in E. coli as inclusion bodies and then solubilized, refolded, and purified using affinity and size-exclusion chromatography. Milligram quantities of pure USP17 can be produced that is catalytically more efficient (kcat/Km = 1500 (x10(3)) M(-1)sec(-1)) than other human USPs studied to date...
December 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27650958/a-conserved-two-step-binding-for-the-uaf1-regulator-to-the-usp12-deubiquitinating-enzyme
#17
Shreya Dharadhar, Marcello Clerici, Willem J van Dijk, Alexander Fish, Titia K Sixma
Regulation of deubiquitinating enzyme (DUB) activity is an essential step for proper function of cellular ubiquitin signals. UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46. Here, we report the crystal structure of the USP12-Ub/UAF1 complex at a resolution of 2.8Å and of UAF1 at 2.3Å. In the complex we find two potential sites for UAF1 binding, analogous to what was seen in a USP46/UAF1 complex. In line with these observed dual binding states, we show here that USP12/UAF1 complex has 1:2 stoichiometry in solution, with a two-step binding at 4nM and 325nM respectively...
December 2016: Journal of Structural Biology
https://www.readbyqxmd.com/read/27620558/developmental-expression-of-ecdysone-related-genes-associated-with-metamorphic-changes-during-midgut-remodeling-of-silkworm-bombyx-mori-lepidoptera-bombycidae
#18
Ebru Goncu, Ramazan Uranlı, Gozde Selek, Osman Parlak
Steroid hormone 20-hydroxyecdysone is known as the systemic regulators of insect cells; however, how to impact the fate and function of mature and stem cells is unclear. For the first time, we report ecdysone regulatory cascades in both mature midgut cell and stem cell fractions related to developmental events by using histological, immunohistochemical, biochemical and gene expression analysis methods. Ecdysone receptor-B1 (EcR-B1) and ultraspiracle 1 (USP-1) mRNAs were detected mainly in mature cells during programmed cell death (PCD)...
2016: Journal of Insect Science
https://www.readbyqxmd.com/read/27618600/internalization-property-of-intestinal-bacteria-in-colon-cancer-and-hiv-aids-patients
#19
Lenka Wachsmannova, Sona Ciernikova, Juraj Majek, Michal Mego, Viola Stevurkova, Vladimir Zajac
OBJECTIVES: Bacteria from the intestinal tract of Slovak and American HIV/AIDS patients and Slovak colon cancer patients were tested for the capacity to be internalized by cells of the HL-60 cell line as well as by normal human lymphocytes. They were anticipated to possess a specific characteristic, i.e. a vigorous ability to be internalized by HL-60 cells and human lymphocytes. This assumption was confirmed by gentamicin protection assay. RESULTS: Internalization of bacteria from HIV/AIDS patients frequently resulted in partial (patients SKM1, SKM22) or complete lysis (patients SKK1-1, SKM12) of HL-60 cells...
July 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/27463890/the-usp1-uaf1-complex-interacts-with-rad51ap1-to-promote-homologous-recombination-repair
#20
Scott Cukras, Euiho Lee, Emily Palumbo, Pamela Benavidez, George-Lucian Moldovan, Younghoon Kee
USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair...
October 2016: Cell Cycle
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