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N-end rule

Benoit Castrec, Cyril Dian, Sarah Ciccone, Coralie L Ebert, Willy V Bienvenut, Jean-Pierre Le Caer, Jean-Marc Steyaert, Carmela Giglione, Thierry Meinnel
An organism's entire protein modification repertoire has yet to be comprehensively mapped. N-myristoylation (MYR) is a crucial eukaryotic N-terminal protein modification. Here we mapped complete Homo sapiens and Arabidopsis thaliana myristoylomes. The crystal structures of human modifier NMT1 complexed with reactive and nonreactive target-mimicking peptide ligands revealed unexpected binding clefts and a modifier recognition pattern. This information allowed integrated mapping of myristoylomes using peptide macroarrays, dedicated prediction algorithms, and in vivo mass spectrometry...
June 11, 2018: Nature Chemical Biology
Ning Liu, Simone N Vigod, M Michèle Farrugia, Marcelo L Urquia, Joel G Ray
BACKGROUND: A woman's risk of venous thromboembolism during pregnancy is estimated to be two-to-six times higher than her risk when she is not pregnant. Such risk estimates are largely based on pregnancies that result in delivery of a newborn baby; no estimates exist for the risk of venous thromboembolism after induced abortion, another common pregnancy outcome. To fill this knowledge gap, we aimed to assess the risk of venous thromboembolism in women whose first pregnancy ended with induced abortion...
June 8, 2018: Lancet Haematology
Geert D'Haens, Walter Reinisch, Remo Panaccione, Jack Satsangi, Joel Petersson, Mareike Bereswill, Dilek Arikan, Eva Perotti, Anne M Robinson, Jasmina Kalabic, Gabriela Alperovich, Roopal Thakkar, Edward V Loftus
OBJECTIVES: Real-world, prospective, long-term studies in Crohn's disease (CD) characterizing adalimumab safety data and lymphoma risk were lacking. We present the final results from the PYRAMID registry, which was designed to rule out a doubling of lymphoma risk in adalimumab-treated patients with CD. METHODS: Patients with moderately to severely active CD newly prescribed or currently receiving adalimumab according to local product labels were followed for up to 6 years and analyzed for adverse events (AEs)...
June 5, 2018: American Journal of Gastroenterology
Mark D White, Jos J A G Kamps, Samuel East, Leah J Taylor Kearney, Emily Flashman
Group VII Ethylene Response Factors (ERF-VIIs) regulate transcriptional adaptation to flooding-induced hypoxia in plants. ERF-VII stability is controlled in an O2 -dependent manner by the Cys/Arg branch of the N-end rule pathway, whereby oxidation of a conserved N-terminal cysteine residue initiates target degradation. This oxidation is catalyzed by Plant Cysteine Oxidases (PCOs) which use O2 as co-substrate to generate Cys-sulfinic acid. The PCOs directly link O2 availability to ERF-VII stability and anaerobic adaptation leading to the suggestion that they act as plant O2 sensors...
May 30, 2018: Journal of Biological Chemistry
Phillip T Durst, Stanley J Moore, Caroline Ritter, Herman W Barkema
Employees, many of whom are not native English speakers, perform the majority of work on large US dairy farms. Although management of employees is a critical role of dairy owners and managers, factors that improve employee engagement and retention are not well known. Objectives were to (1) identify key dairy farm employee management issues based on employee perceptions, (2) evaluate strengths and weaknesses of farms based on employee responses, (3) investigate differences between Latino and English-speaking employees, and (4) investigate differences in perception between employers and employees...
May 23, 2018: Journal of Dairy Science
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
Rosagemma Ciliberti, Matteo Gulino, Ilaria Gorini
The Italian Parliament has recently approved the Law n. 219/2017 concerning "Rules on informed consent and advance directives". The manuscript points out the main key points of the new law, in order to clarify the role of the advance directives and to provide clear operational guidelines for healthcare personnel. Taking into consideration the Italian deontological and juridical context, along with the main jurisprudential judgements, the law has been analysed. The Authors discussed the new rules and the bioethical issues also in relation to the provisions stated by the Convention on Human Rights and Biomedicine (Convention of Oviedo)...
May 2018: Recenti Progressi in Medicina
Anna Green, Natalia Jerzmanowska, Marguerite Green, Elizabeth A Lobb
BACKGROUND: Ethnic minority patients have unique challenges in accessing health services. These include language difficulties, unfamiliarity with the health system, lower rates of cancer screening and survival, higher rates of reported side effects from cancer treatment and poorer quality of life. Little is known about this patient group when transitioning to palliative care. AIM: To elicit the experiences of palliative care health professionals when providing care for patients from culturally and linguistically diverse backgrounds which differ from mainstream Australian language and culture...
May 1, 2018: Palliative Medicine
Nan Zhao, Chuanwei Li, Yajun Yan, Wen Cao, Aiping Song, Haibin Wang, Sumei Chen, Jiafu Jiang, Fadi Chen
Waterlogging stress is among the most severe abiotic stressors in the breeding and the production of Chrysanthemum morifolium. However, the mechanism underlying the response to waterlogging and post-waterlogging reoxygenation in C. morifolium remains unknown. In this study, we compared the differences between the transcriptomes of two chrysanthemum cultivars, i.e., the waterlogging-tolerant cultivar "Nannongxuefeng" and the waterlogging-sensitive cultivar "Qinglu", by performing RNA-seq to elucidate the possible mechanism of waterlogging and reoxygenation in C...
May 14, 2018: International Journal of Molecular Sciences
Ilia Kats, Anton Khmelinskii, Marc Kschonsak, Florian Huber, Robert A Knieß, Anna Bartosik, Michael Knop
Most eukaryotic proteins are N-terminally acetylated. This modification can be recognized as a signal for selective protein degradation (degron) by the N-end rule pathways. However, the prevalence and specificity of such degrons in the proteome are unclear. Here, by systematically examining how protein turnover is affected by N-terminal sequences, we perform a comprehensive survey of degrons in the yeast N-terminome. We find that approximately 26% of nascent protein N termini encode cryptic degrons. These degrons exhibit high hydrophobicity and are frequently recognized by the E3 ubiquitin ligase Doa10, suggesting a role in protein quality control...
May 3, 2018: Molecular Cell
David A Dougan, Alexander Varshavsky
No abstract text is available yet for this article.
May 2018: Nature Chemical Biology
Christine M Bestvina, Kristen E Wroblewski, Bobby Daly, Brittany Beach, Selina Chow, Andrew Hantel, Monica Malec, Michael T Huber, Blase N Polite
BACKGROUND: Accurate understanding of the prognosis of an advanced cancer patient can lead to decreased aggressive care at the end of life and earlier hospice enrollment. OBJECTIVE: Our goal was to determine the association between high-risk clinical events identified by a simple, rules-based algorithm and decreased overall survival, to target poor prognosis cancer patients who would urgently benefit from advanced care planning. DESIGN: A retrospective analysis was performed on outpatient oncology patients with an index visit from April 1, 2015, through June 30, 2015...
March 13, 2018: Journal of Palliative Medicine
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 2018: PLoS Genetics
Angela Wulff, Maria Karlberg, Malin Olofsson, Anders Torstensson, Lasse Riemann, Franciska S Steinhoff, Malin Mohlin, Nina Ekstrand, Melissa Chierici
Helcom scenario modelling suggests that the Baltic Sea, one of the largest brackish-water bodies in the world, could expect increased precipitation (decreased salinity) and increased concentration of atmospheric CO2 over the next 100 years. These changes are expected to affect the microplanktonic food web, and thereby nutrient and carbon cycling, in a complex and possibly synergistic manner. In the Baltic Proper, the extensive summer blooms dominated by the filamentous cyanobacteria Aphanizomenon sp., Dolichospermum spp...
2018: Marine Biology
Kai Zheng, Qiuying Liu, Shaoxiang Wang, Zhe Ren, Kaio Kitazato, Depo Yang, Yifei Wang
Herpes simplex virus 1 (HSV-1) encodes various microRNAs (miRNAs), whose targets are largely unknown. miR-H1 is the first discovered HSV-1 miRNA and is expressed predominantly in productive infection. Here we show that ubiquitin protein ligase E3 component n-recognin 1 (Ubr1) is a cellular target of miR-H1. Ubr1 is a RING-type E3 ubiquitin ligase of the Arg/N-end rule pathway, which causes the degradation of proteins bearing "destabilizing" N-terminal residues, such as neurodegeneration-associated protein fragment β-amyloid...
June 2018: Virus Genes
Anna Starshinova, Viacheslav Zhuravlev, Irina Dovgaluk, Alexandr Panteleev, Vera Manina, Ulia Zinchenko, Evgenia Istomina, Maria Pavlova, Piotr Yablonskiy
Background: The WHO strategy for eradication of tuberculosis (TB) by 2035 (The End TB Strategy) is aimed at an early and precise diagnosis and subsequent effective treatment of TB patients. Currently, there is no gold standard for the diagnosis of latent TB infection. This study evaluated the diagnostic capabilities of a new intradermal test using recombinant TB allergen (Diaskintest) compared with tuberculin skin test (TST) and commercial TB interferon-gamma release assays (IGRAs). Methods: A post-hoc data analysis that involved examining 860 HIV-negative, bacillus Calmette-Guérin (BCG)-vaccinated persons aged 1-65 years who visited the TB health-care institutions of Saint Petersburg to rule out or confirm an active TB was conducted from 2011 to 2016...
January 2018: International Journal of Mycobacteriology
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 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Clara V Colombo, Germán L Rosano, Axel Mogk, Eduardo A Ceccarelli
Proteins that are to be eliminated must be proficiently recognized by proteolytic systems so that inadvertent elimination of useful proteins is avoided. One mechanism to ensure proper recognition is the presence of N-terminal degradation signals (N-degrons) that are targeted by adaptor proteins (N-recognins). The members of the caseinolytic protease S (ClpS) family of N-recognins identify targets bearing an N-terminal phenylalanine, tyrosine, tryptophan or leucine residue, and then present them to a protease system...
March 1, 2018: Plant & Cell Physiology
Qing Luan, Alex Zelter, Michael J MacCoss, Trisha N Davis, Brad J Nolen
Arp2/3 complex nucleates branched actin filaments important for cellular motility and endocytosis. WASP family proteins are Arp2/3 complex activators that play multiple roles in branching nucleation, but little is known about the structural bases of these WASP functions, owing to an incomplete understanding of how WASP binds Arp2/3 complex. Recent data show WASP binds two sites, and biochemical and structural studies led to models in which the WASP C segment engages the barbed ends of the Arp3 and Arp2 subunits while the WASP A segment binds the back side of the complex on Arp3...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Leo F Buckley, Justin M Canada, Marco G Del Buono, Salvatore Carbone, Cory R Trankle, Hayley Billingsley, Dinesh Kadariya, Ross Arena, Benjamin W Van Tassell, Antonio Abbate
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that presents clinicians with a diagnostic challenge. The use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) level above and below the proposed cut-off. METHODS: Stable patients (n = 30) with left ventricular (LV) ejection fraction ≥ 50% were eligible if they had a diagnosis of HF according to the European Society of Cardiology diagnostic criteria...
January 18, 2018: ESC Heart Failure
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