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Jyothsna Chitturi, Wesley Hung, Anas M Abdel Rahman, Min Wu, Maria A Lim, John Calarco, Renee Baran, Xun Huang, James W Dennis, Mei Zhen
UBR1 is an E3 ubiquitin ligase best known for its ability to target protein degradation by the N-end rule. The physiological functions of UBR family proteins, however, remain not fully understood. We found that the functional loss of C. elegans UBR-1 leads to a specific motor deficit: when adult animals generate reversal movements, A-class motor neurons exhibit synchronized activation, preventing body bending. This motor deficit is rescued by removing GOT-1, a transaminase that converts aspartate to glutamate...
April 12, 2018: PLoS Genetics
Xavier Borrat, Marta Ubre, Raquel Risco, Pedro L Gambús, Angela Pedroso, Aina Iglesias, Gloria Fernandez-Esparrach, Àngels Ginés, Jaume Balust, Graciela Martínez-Palli
The use of sedation for diagnostic procedures including gastrointestinal endoscopy is rapidly growing. Recovery of cognitive function after sedation is important because it would be important for most patients to resume safe, normal life soon after the procedure. Computerized tests have shown being accurate descriptors of cognitive function. The purpose of the present study was to evaluate the time course of cognitive function recovery after sedation with propofol and remifentanil. A prospective observational double blind clinical study conducted in 34 young healthy adults undergoing elective outpatient colonoscopy under sedation with the combination of propofol and remifentanil using a target controlled infusion system...
March 27, 2018: Journal of Clinical Monitoring and Computing
Young Dong Yoo, Su Ran Mun, Chang Hoon Ji, Ki Woon Sung, Keum Young Kang, Ah Jung Heo, Su Hyun Lee, Jee Young An, Joonsung Hwang, Xiang-Qun Xie, Aaron Ciechanover, Bo Yeon Kim, Yong Tae Kwon
The conjugation of amino acids to the protein N termini is universally observed in eukaryotes and prokaryotes, yet its functions remain poorly understood. In eukaryotes, the amino acid l-arginine (l-Arg) is conjugated to N-terminal Asp (Nt-Asp), Glu, Gln, Asn, and Cys, directly or associated with posttranslational modifications. Following Nt-arginylation, the Nt-Arg is recognized by UBR boxes of N-recognins such as UBR1, UBR2, UBR4/p600, and UBR5/EDD, leading to substrate ubiquitination and proteasomal degradation via the N-end rule pathway...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Morgan M Sellers, Luke J Keele, Catherine E Sharoky, Christopher Wirtalla, Elizabeth A Bailey, Rachel R Kelz
Importance: Important metrics of residency program success include the clinical outcomes achieved by trainees after transitioning to practice. Previous studies have shown significant differences in reported training experiences of general surgery residents at nonuniversity-based residency (NUBR) and university-based residency (UBR) programs. Objective: To examine the differences in practice patterns and clinical outcomes between surgeons trained in NUBR and those trained in UBR programs...
January 10, 2018: JAMA Surgery
Juliana Muñoz-Escobar, Guennadi Kozlov, Kalle Gehring
The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold...
October 2017: Protein Science: a Publication of the Protein Society
Benjamin P Weaver, Yi M Weaver, Shohei Mitani, Min Han
Recent findings suggest that components of the classical cell death machinery also have important non-cell-death (non-apoptotic) functions in flies, nematodes, and mammals. However, the mechanisms for non-canonical caspase substrate recognition and proteolysis, and the direct roles for caspases in gene expression regulation, remain largely unclear. Here we report that CED-3 caspase and the Arg/N-end rule pathway cooperate to inactivate the LIN-28 pluripotency factor in seam cells, a stem-like cell type in Caenorhabditis elegans, thereby ensuring proper temporal cell fate patterning...
June 19, 2017: Developmental Cell
F Dana, D Capitán, M Ubré, A Hervás, R Risco, G Martínez-Pallí
INTRODUCTION: Frailty and low physical activity and cardiorespiratory reserve are related to higher perioperative morbimortality. The crucial step in improving the prognosis is to implement specific measures to optimize these aspects. It is critical to know the magnitude of the problem in order to implement preoperative optimization programmes. OBJECTIVE: To characterize surgical population in a university hospital. METHODS: All patients undergoing preoperative evaluation for abdominal surgery with admission were prospectively included during a 3-month period...
January 2018: Revista Española de Anestesiología y Reanimación
Yuanyuan Yang, Li Shi, Yiluan Ding, Yanhong Shi, Hong-Yu Hu, Yi Wen, Naixia Zhang
Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well...
May 23, 2017: Biophysical Journal
Anael Barberan-Garcia, Marta Ubré, Josep Roca, Antonio M Lacy, Felip Burgos, Raquel Risco, Dulce Momblán, Jaume Balust, Isabel Blanco, Graciela Martínez-Pallí
OBJECTIVE: The aim of this study was to assess the impact of personalized prehabilitation on postoperative complications in high-risk patients undergoing elective major abdominal surgery. SUMMARY BACKGROUND DATA: Prehabilitation, including endurance exercise training and promotion of physical activity, in patients undergoing major abdominal surgery has been postulated as an effective preventive intervention to reduce postoperative complications. However, the existing studies provide controversial results and show a clear bias toward low-risk patients...
January 2018: Annals of Surgery
Juliana Muñoz-Escobar, Edna Matta-Camacho, Cordelia Cho, Guennadi Kozlov, Kalle Gehring
The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides...
May 2, 2017: Structure
Komal Safdar, Anniya Gu, Xia Xu, Vinci Au, Jon Taylor, Stephane Flibotte, Donald G Moerman, Eleanor M Maine
Notch-type signaling mediates cell-cell interactions important for animal development. In humans, reduced or inappropriate Notch signaling activity is associated with various developmental defects and disease states, including cancers. Caenorhabditis elegans expresses two Notch-type receptors, GLP-1 and LIN-12. GLP-1 mediates several cell-signaling events in the embryo and promotes germline proliferation in the developing and adult gonad. LIN-12 acts redundantly with GLP-1 in certain inductive events in the embryo and mediates several cell-cell interactions during larval development...
July 7, 2016: G3: Genes—Genomes—Genetics
Clinton Yu, Yingying Yang, Xiaorong Wang, Shenheng Guan, Lei Fang, Fen Liu, Kylie J Walters, Peter Kaiser, Lan Huang
Proteasomes are protein degradation machines that exist in cells as heterogeneous and dynamic populations. A group of proteins function as ubiquitin receptors (UbRs) that can recognize and deliver ubiquitinated substrates to proteasome complexes for degradation. Defining composition of proteasome complexes engaged with UbRs is critical to understand proteasome function. However, because of the dynamic nature of UbR interactions with the proteasome, it remains technically challenging to capture and isolate UbR-proteasome subcomplexes using conventional purification strategies...
July 2016: Molecular & Cellular Proteomics: MCP
M G Vinciguerra, G Belcaro, M Cacchio
AIM: The aim of this registry study was to evaluate the effects of supplementation with Robuvit® (Quercus robur wood extract, or "QR") on performance and endurance in triathlon by evaluating amateur athletes in a period of 2 weeks of training. Supplementation with QR may improve training efficiency (by decreasing post-triathlon, muscular pain, cramps and by improving recovery time). Robuvit® should decrease post-training plasma free radicals (PFR). METHODS: Sixty-one subjects (age range 30-40) were included in the study...
October 2015: Minerva Cardioangiologica
Kenji Kitamura
Ubr11 in the fission yeast Schizosaccharomyces pombe is an evolutionarily conserved ubiquitin ligase functioning in the Arg/N-end rule pathway, which promotes degradation of substrate proteins via the proteasome. Ubr11 recognizes the N-degron sequence in substrates. The primary N-degron contains a destabilization-inducing N-terminal amino acid, which is either a basic (type 1) or bulky hydrophobic (type 2) residue. Dipeptides are known to inhibit proteolytic degradation via the Arg/N-end rule pathway. Here, I examined the potency of some amino acid- or dipeptide-related molecules in their inhibition of Ubr11/N-end rule-mediated degradation...
January 2016: Amino Acids
Yi Wen, Li Shi, Yiluan Ding, Rong Cui, Wen-tian He, Hong-yu Hu, Naixia Zhang
The deubiquitinase ubiquitin-specific protease 28 (Usp28) contains a ubiquitin-binding region (UBR) composed of one ubiquitin-associated domain (UBA) and one ubiquitin-interacting motif (UIM) at its N-terminus. It is of interest that an additional small ubiquitin-like modifier (SUMO)-interacting motif (SIM) is located next to its UIM. To date, the functional role of the Usp28 UBR is still not understood. To elucidate the regulatory mechanism of the UBR on the full functional display of Usp28, in the present study, NMR and biochemical approaches were applied...
October 15, 2015: Biochemical Journal
Gurmeet Kaur, Srikrishna Subramanian
BACKGROUND: The N-end rule pathway is a part of the ubiquitin-dependent proteolytic system wherein N-recognin proteins recognize the amino terminal degradation signals (N-degrons) of the substrate. The type 1 N-degron recognizing UBR-box domain of the eukaryotic Arg/N-end rule pathway is known to possess a novel three-zinc-stabilized heart-shaped fold. RESULTS: Using sequence and structure analysis we argue that the UBR-box fold emerged from a binuclear RING-like treble clef zinc finger...
July 17, 2015: Biology Direct
Chunxia Zhao, Lijie Wang, Xiue Ma, Weidong Zhu, Lei Yao, Yingyu Cui, Yi Liu, Jun Li, Xingqun Liang, Yunfu Sun, Li Li, Yi-Han Chen
The voltage-gated Na(+) channel Nav 1.5 is essential for action potential (AP) formation and electrophysiological homoeostasis in the heart. The ubiquitin-proteasome system (UPS) is a major degradative system for intracellular proteins including ion channels. The ubiquitin protein ligase E3 component N-recognin (UBR) family is a part of the UPS; however, their roles in regulating cardiac Nav 1.5 channels remain elusive. Here, we found that all of the UBR members were expressed in cardiomyocytes. Individual knockdown of UBR3 or UBR6, but not of other UBR members, significantly increased Nav 1...
September 2015: Journal of Cellular and Molecular Medicine
Kenji Kitamura
Several Ubr ubiquitin ligases recognize the N-terminal amino acid of substrate proteins and promote their degradation via the Arg/N-end rule pathway. The primary destabilizing N-terminal amino acids in yeast are classified into type 1 (Arg, Lys, and His) and type 2 (Phe, Trp, Tyr, Leu, Ile, and Met-Ф) residues. The type 1 and type 2 residues bind to the UBR box and the ClpS/N-domain, respectively, in canonical Ubr ubiquitin ligases that act as N-recognins. In this study, the requirement for type 1 and type 2 amino acid recognition by Schizosaccharomyces pombe Ubr11 was examined in vivo...
2014: SpringerPlus
Cheng-Yi Chang, Jian-Ri Li, Wen-Ying Chen, Yen-Chuan Ou, Ching-Yi Lai, Yu-Hui Hu, Chih-Cheng Wu, Chen-Jung Chang, Chun-Jung Chen
Blood-brain barrier (BBB) characteristics are induced and maintained by crosstalk between brain microvascular endothelial cells and neighboring cells. Using in vitro cell models, we previously found that a bystander effect was a cause for Japanese encephalitis-associated endothelial barrier disruption. Brain astrocytes, which neighbor BBB endothelial cells, play roles in the maintenance of BBB integrity. By extending the scope of relevant studies, a potential mechanism has been shown that the activation of neighboring astrocytes could be a cause of disruption of endothelial barrier integrity during the course of Japanese encephalitis viral (JEV) infection...
May 8, 2015: Glia
Lluís Fumadó, Lluís Cecchini, Nuria Juanpere, Anna Ubré, Jose Antonio Lorente, Antonio Alcaraz
INTRODUCTION: To determine whether unilateral prostate cancer diagnosed at 12-core prostate biopsy harbours relevant prostate cancer foci in contralateral lobe in cases eligible for hemiablative focal therapy. MATERIAL AND METHODS: We analysed 112 radical prostatectomies of unilateral Gleason 6/7 prostate cancer based on prostate biopsy information. The presence of significant prostate cancer foci and/or the index lesion in the contralateral lobe is described. A subanalysis is performed in cases of Gleason score 6 and in cases of very-low-risk prostate cancer...
2015: Urologia Internationalis
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