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ubiquitination,ubiquitin

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https://www.readbyqxmd.com/read/30137960/reprogramming-a-deubiquitinase-into-a-transamidase
#1
Lin Hui Chang, Eric R Strieter
Access to well-defined ubiquitin conjugates has been key to elucidating the biochemical functions of proteins in the ubiquitin signaling network. Yet, we have a poor understanding of how deubiquitinases and ubiquitin-binding proteins respond to ubiquitin modifications when anchored to a protein other than ubiquitin or a ubiquitin-like protein. This is due to the difficulty of synthesizing ubiquitinated proteins comprised of native isopeptide bonds. Here we report on the evolution of a deubiquitinase capable of site-specifically modifying itself with defined ubiquitin chains...
September 21, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/30086823/comparative-analysis-of-testis-transcriptomes-associated-with-male-infertility-in-triploid-cyprinid-fish
#2
Wuhui Li, Hui Tan, Junmei Liu, Jie Hu, Jialin Cui, Shi Wang, Qingfeng Liu, Fangzhou Hu, Li Ren, Min Tao, Rurong Zhao, Conghui Yang, Qinbo Qin, Shaojun Liu
Spermatogenesis involves a series of cellular transformations and thousands of regulated genes. Previously, we showed that the triploid fish (3nBY) cannot produce mature spermatozoa. In the present study, evaluation of the testis microstructure revealed that germ cells of 3nBY could develop into round spermatids, but then degenerated, resulting in male infertility. In this study we comparatively analysed the testis transcriptomes from 3nBY and its diploid parent YB and identified a series of differentially expressed genes (DEGs) that were enriched in the Wnt signalling pathway and the apoptotic and ubiquitin-mediated proteolysis processes in 3nBY...
August 8, 2018: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29846841/an-update-on-autoinflammatory-diseases-relopathies
#3
REVIEW
Annemarie Steiner, Cassandra R Harapas, Seth L Masters, Sophia Davidson
PURPOSE OF REVIEW: The nuclear factor κB (NF-κB) pathway is tightly regulated through multiple posttranslational mechanisms including ubiquitination. Mutations in these regulatory pathways can cause disease and are the focus of this review. RECENT FINDINGS: The linear ubiquitin chain assembly complex (LUBAC) is a trimer made up of HOIL-1L, SHARPIN, and the catalytic subunit HOIP. Loss of function mutations in HOIL-1L and HOIP result in largely overlapping phenotypes, characterized by multi-organ autoinflammation, immunodeficiency, and amylopectinosis...
May 30, 2018: Current Rheumatology Reports
https://www.readbyqxmd.com/read/29760280/monoubiquitination-of-cancer-stem-cell-marker-cd133-at-lysine-848-regulates-its-secretion-and-promotes-cell-migration
#4
Fan Yang, Yang Xing, Yinan Li, Xiaoning Chen, Jianhai Jiang, Zhilong Ai, Yuanyan Wei
CD133, a widely known marker of cancer stem cells, was recently found in extracellular vesicles. However, the mechanisms underlying CD133 translocation to the extracellular space remain largely unknown. Here we report that CD133 is monoubiquitinated. Ubiquitination occurs primarily on complex glycosylated CD133. The lysine 848 residue at the intracellular carboxyl terminus is one of the sites for CD133 ubiquitination. The K848R mutation does not affect CD133 degradation by the lysosomal pathway but significantly reduces CD133 secretion by inhibiting the interaction between CD133 and tumor susceptibility gene 101 (Tsg101)...
August 1, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29723144/-ubiquitin-independent-protein-degradation-in-proteasomes
#5
REVIEW
O A Buneeva, A E Medvedev
Proteasomes are large supramolecular protein complexes present in all prokaryotic and eukaryotic cells, where they perform targeted degradation of intracellular proteins. Until recently, it was generally accepted that prior proteolytic degradation in proteasomes the proteins had to be targeted by ubiquitination: the ATP-dependent addition of (typically four sequential) residues of the low-molecular ubiquitin protein, involving the ubiquitin-activating enzyme, ubiquitin-conjugating enzyme and ubiquitin ligase...
March 2018: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29518557/transcriptome-analyses-reveal-litopenaeus-vannamei-hemocytes-response-to-lipopolysaccharide
#6
Yueling Zhang, Guicai Gao, Ruihong Lin, Jude Juventus Aweya, Mengyuan Tao, Fan Wang
Although vertebrate immunity has been well studied for the past decades, invertebrate immunity was much less explored. One possible reason was that in vitro culture system was not well established. In this study, Litopenaeus vannamei was applied as an invertebrate study model. Primary culture conditions for L. vannamei hemocytes were optimized to get relatively quiescent state cells. LPS was used as an immune stimulator and the responses of primary cultured hemocytes were transcriptomically analyzed. Our results showed that around 1,600 genes were upregulated and 800 genes were downregulated from LPS treated hemocytes...
May 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29106644/iuucd-2-0-an-update-with-rich-annotations-for-ubiquitin-and-ubiquitin-like-conjugations
#7
Jiaqi Zhou, Yang Xu, Shaofeng Lin, Yaping Guo, Wankun Deng, Ying Zhang, Anyuan Guo, Yu Xue
Here, we described the updated database iUUCD 2.0 (http://iuucd.biocuckoo.org/) for ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), ubiquitin-protein ligases (E3s), deubiquitinating enzymes (DUBs), ubiquitin/ubiquitin-like binding domains (UBDs) and ubiquitin-like domains (ULDs), which act as key regulators in modulating ubiquitin and ubiquitin-like (UB/UBL) conjugations. In total, iUUCD 2.0 contained 136 512 UB/UBL regulators, including 1230 E1s, 5636 E2s, 93 343 E3s, 9548 DUBs, 30 173 UBDs and 11 099 ULDs in 148 eukaryotic species...
January 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/28972311/viral-oncoproteins-and-ubiquitination-accessing-a-cellular-toolbox-for-modifying-protein-function
#8
COMMENT
Miranda Thomas, Lawrence Banks
Human Papillomavirus oncoproteins directly target components of the Ubiquitin Proteasome System (UPS) and allow perturbation of multiple cellular processes linked to the control of apoptosis, transcription and innate immunity. This activity primarily creates an environment favourable for viral replication, but can contribute towards malignancy, thus highlighting the roles that manipulation of the UPS can play in the development of human cancers.
October 2017: FEBS Journal
https://www.readbyqxmd.com/read/28957379/involvement-of-parkin-in-the-ubiquitin-proteasome-system-mediated-degradation-of-n-type-voltage-gated-ca2-channels
#9
Lizbeth Grimaldo, Alejandro Sandoval, Edgar Garza-López, Ricardo Felix
N-type calcium (CaV2.2) channels are widely expressed in the brain and the peripheral nervous system, where they play important roles in the regulation of transmitter release. Although CaV2.2 channel expression levels are precisely regulated, presently little is known regarding the molecules that mediate its synthesis and degradation. Previously, by using a combination of biochemical and functional analyses, we showed that the complex formed by the light chain 1 of the microtubule-associated protein 1B (LC1-MAP1B) and the ubiquitin-proteasome system (UPS) E2 enzyme UBE2L3, may interact with the CaV2...
2017: PloS One
https://www.readbyqxmd.com/read/28943312/ubiquitin-linkage-specific-affimers-reveal-insights-into-k6-linked-ubiquitin-signaling
#10
Martin A Michel, Kirby N Swatek, Manuela K Hospenthal, David Komander
Several ubiquitin chain types have remained unstudied, mainly because tools and techniques to detect these posttranslational modifications are scarce. Linkage-specific antibodies have shaped our understanding of the roles and dynamics of polyubiquitin signals but are available for only five out of eight linkage types. We here characterize K6- and K33-linkage-specific "affimer" reagents as high-affinity ubiquitin interactors. Crystal structures of affimers bound to their cognate chain types reveal mechanisms of specificity and a K11 cross-reactivity in the K33 affimer...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28943310/asf1a-promotes-non-homologous-end-joining-repair-by-facilitating-phosphorylation-of-mdc1-by-atm-at-double-strand-breaks
#11
Kyung Yong Lee, Jun-Sub Im, Etsuko Shibata, Anindya Dutta
Double-strand breaks (DSBs) of DNA in eukaryotic cells are predominantly repaired by non-homologous end joining (NHEJ). The histone chaperone anti-silencing factor 1a (ASF1a) interacts with MDC1 and is recruited to sites of DSBs to facilitate the interaction of phospho-ATM with MDC1 and phosphorylation of MDC1, which are required for the recruitment of RNF8/RNF168 histone ubiquitin ligases. Thus, ASF1a deficiency reduces histone ubiquitination at DSBs, decreasing the recruitment of 53BP1, and decreases NHEJ, rendering cells more sensitive to DSBs...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28934429/gene-expression-analysis-reveals-genes-common-to-cerebral-malaria-and-neurodegenerative-disorders
#12
Sandrine Cabantous, Ogobara Doumbo, Belco Poudiougou, Laurence Louis, Abdoulaye Barry, Aboubacar A Oumar, Abdoualye Traore, Sandrine Marquet, Alain Dessein
Cerebral malaria, a reversible encephalopathy affecting young children, is a medical emergency requiring urgent clinical assessment and treatment. We performed a whole-transcriptomic analysis of blood samples from Malian children with cerebral or uncomplicated malaria. We focused on transcripts from pathways for which dysfunction has been associated with neurodegenerative disorders. We found that SNCA, SIAH2, UBB, HSPA1A, TUBB2A, and PINK1 were upregulated (fold-increases, ≥2.6), whereas UBD and PSMC5 were downregulated (fold-decreases, ≤4...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28910856/high-throughput-screening-of-hect-e3-ubiquitin-ligases-using-ubfluor
#13
Peter K Foote, David T Krist, Alexander V Statsyuk
HECT E3 ubiquitin ligases are responsible for many human disease phenotypes and are promising drug targets; however, screening assays for HECT E3 inhibitors are inherently complex, requiring upstream E1 and E2 enzymes as well as ubiquitin, ATP, and detection reagents. Intermediate ubiquitin thioesters and a complex mixture of polyubiquitin products provide further opportunities for off-target inhibition and increase the complexity of the assay. UbFluor is a novel ubiquitin thioester that bypasses the E1 and E2 enzymes and undergoes direct transthiolation with HECT E3 ligases...
September 14, 2017: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/28893839/mitochondrial-fission-facilitates-the-selective-mitophagy-of-protein-aggregates
#14
Jonathon L Burman, Sarah Pickles, Chunxin Wang, Shiori Sekine, Jose Norberto S Vargas, Zhe Zhang, Alice M Youle, Catherine L Nezich, Xufeng Wu, John A Hammer, Richard J Youle
Within the mitochondrial matrix, protein aggregation activates the mitochondrial unfolded protein response and PINK1-Parkin-mediated mitophagy to mitigate proteotoxicity. We explore how autophagy eliminates protein aggregates from within mitochondria and the role of mitochondrial fission in mitophagy. We show that PINK1 recruits Parkin onto mitochondrial subdomains after actinonin-induced mitochondrial proteotoxicity and that PINK1 recruits Parkin proximal to focal misfolded aggregates of the mitochondrial-localized mutant ornithine transcarbamylase (ΔOTC)...
October 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28860335/activation-mechanisms-of-the-e3-ubiquitin-ligase-parkin
#15
REVIEW
Nikhil Panicker, Valina L Dawson, Ted M Dawson
Monogenetic, familial forms of Parkinson's disease (PD) only account for 5-10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin , encodes a 465 amino acid E3 ubiquitin ligase. Of late, there has been considerable interest in the role of parkin signaling in PD and in identifying its putative substrates, as well as the elucidation of the mechanisms through which parkin itself is activated...
August 30, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28844860/an-aaa-motor-driven-mechanical-switch-in-rpn11-controls-deubiquitination-at-the-26s-proteasome
#16
Evan J Worden, Ken C Dong, Andreas Martin
Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to prevent premature ubiquitin chain removal and substrate escape. Here we reveal the ubiquitin-bound structure of Rpn11 from S. cerevisiae and the mechanisms for mechanochemical coupling of substrate degradation and deubiquitination...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28786561/mapping-the-interactome-of-hpv-e6-and-e7-oncoproteins-with-the-ubiquitin-proteasome-system
#17
EDITORIAL
Juline Poirson, Elise Biquand, Marie-Laure Straub, Patricia Cassonnet, Yves Nominé, Louis Jones, Sylvie van der Werf, Gilles Travé, Katia Zanier, Yves Jacob, Caroline Demeret, Murielle Masson
Protein ubiquitination and its reverse reaction, deubiquitination, regulate protein stability, protein binding activity, and their subcellular localization. These reactions are catalyzed by the enzymes E1, E2, and E3 ubiquitin (Ub) ligases and deubiquitinases (DUBs). The Ub-proteasome system (UPS) is targeted by viruses for the sake of their replication and to escape host immune response. To identify novel partners of human papillomavirus 16 (HPV16) E6 and E7 proteins, we assembled and screened a library of 590 cDNAs related to the UPS by using the Gaussia princeps luciferase protein complementation assay...
October 2017: FEBS Journal
https://www.readbyqxmd.com/read/28771691/targeting-hect-type-e3-ligases-insights-from-catalysis-regulation-and-inhibitors
#18
REVIEW
Valentina Fajner, Elena Maspero, Simona Polo
Ubiquitination plays a pivotal role in most cellular processes and is critical for protein degradation and signalling. E3 ligases are the matchmakers in the ubiquitination cascade, responsible for substrate recognition and modification with specific polyubiquitin chains. Until recently, it was not clear how the catalytic activity of E3s is modulated, but major recent studies on HECT E3 ligases is filling this void. These enzymes appear to be held in a closed, inactive conformation, which is relieved by biochemical manoeuvres unique to each member, thus ensuring exquisite regulation and specificity of the enzymes...
September 2017: FEBS Letters
https://www.readbyqxmd.com/read/28768733/central-catalytic-domain-of-brap-rnf52-recognizes-the-types-of-ubiquitin-chains-and-utilizes-oligo-ubiquitin-for-ubiquitylation
#19
Shisako Shoji, Kazuharu Hanada, Noboru Ohsawa, Mikako Shirouzu
Really interesting new gene (RING)-finger protein 52 (RNF52), an E3 ubiquitin ligase, is found in eukaryotes from yeast to humans. Human RNF52 is known as breast cancer type 1 susceptibility protein (BRCA1)-associated protein 2 (BRAP or BRAP2). The central catalytic domain of BRAP comprises four subdomains: nucleotide-binding α/β plait (NBP), really interesting new gene (RING) zinc finger, ubiquitin-specific protease (UBP)-like zinc finger (ZfUBP), and coiled-coil (CC). This domain architecture is conserved in RNF52 orthologs; however, the domain's function in the ubiquitin system has not been delineated...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28754446/selection-of-reliable-reference-genes-for-gene-expression-studies-in-trichoderma-afroharzianum-ltr-2-under-oxalic-acid-stress
#20
Yuping Lyu, Xiaoqing Wu, He Ren, Fangyuan Zhou, Hongzi Zhou, Xinjian Zhang, Hetong Yang
An appropriate reference gene is required to get reliable results from gene expression analysis by quantitative real-time reverse transcription PCR (qRT-PCR). In order to identify stable and reliable reference genes in Trichoderma afroharzianum under oxalic acid (OA) stress, six commonly used housekeeping genes, i.e., elongation factor 1, ubiquitin, ubiquitin-conjugating enzyme, glyceraldehyde-3-phosphate dehydrogenase, α-tubulin, actin, from the effective biocontrol isolate T. afroharzianum strain LTR-2 were tested for their expression during growth in liquid culture amended with OA...
October 2017: Journal of Microbiological Methods
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