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Ubiquitination

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https://www.readbyqxmd.com/read/28813668/subnuclear-relocalization-of-structure-specific-endonucleases-in-response-to-dna-damage
#1
Irene Saugar, Alberto Jiménez-Martín, José Antonio Tercero
Structure-specific endonucleases contribute to the maintenance of genome integrity by cleaving DNA intermediates that need to be resolved for faithful DNA repair, replication, or recombination. Despite advances in the understanding of their function and regulation, it is less clear how these proteins respond to genotoxic stress. Here, we show that the structure-specific endonuclease Mus81-Mms4/EME1 relocalizes to subnuclear foci following DNA damage and colocalizes with the endonucleases Rad1-Rad10 (XPF-ERCC1) and Slx1-Slx4...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813603/modeling-optical-spectra-of-large-organic-systems-using-real-time-propagation-of-semiempirical-effective-hamiltonians
#2
Soumen Ghosh, Amity Andersen, Laura Gagliardi, Christopher J Cramer, Niranjan Govind
We present an implementation of a time-dependent semiempirical method (INDO/S) in NWChem using real-time (RT) propagation to address, in principle, the entire spectrum of valence electronic excitations. Adopting this model, we study the UV-visible spectra of medium-sized systems like P3B2, f-coronene, and in addition much larger systems like ubiquitin in the gas phase and the betanin chromophore in the presence of two explicit solvents (water and methanol). RT-INDO/S provides qualitatively and indeed often quantitatively accurate results when compared with RT- TDDFT or experimental spectra...
August 16, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28813410/identification-of-cmtm6-and-cmtm4-as-pd-l1-protein-regulators
#3
Riccardo Mezzadra, Chong Sun, Lucas T Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Meike E W Logtenberg, Maarten Slagter, Elisa A Rozeman, Ingrid Hofland, Annegien Broeks, Hugo M Horlings, Lodewyk F A Wessels, Christian U Blank, Yanling Xiao, Albert J R Heck, Jannie Borst, Thijn R Brummelkamp, Ton N M Schumacher
The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813181/pathway-choice-between-proteasomal-and-autophagic-degradation
#4
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Efficient degradation of abnormal or aggregated proteins is crucial to protect the cell against proteotoxic stress. Selective targeting and disposal of such proteins usually occurs in a ubiquitin-dependent manner by proteasomes and macroautophagy/autophagy. Whereas proteasomes are efficient in degrading abnormal soluble proteins, protein aggregates are typically targeted for degradation by autophagic vesicles. Both processes require ubiquitin-binding receptors, which are targeted to proteasomes via ubiquitin-like domains or to phagophores (the precursors to autophagosomes) via Atg8/LC3 binding motifs, respectively...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812433/regulation-of-sqstm1-p62-via-uba-domain-ubiquitination-and-its-role-in-disease
#5
YouJin Lee, Conrad C Weihl
Macroautophagy/autophagy can be a selective degradative process via the utilization of various autophagic receptor proteins. Autophagic receptors selectively recognize ubiquitinated cargoes and deliver them to phagophores, the precursors to autophagosomes, for their degradation. For example, SQSTM1/p62 directly binds to ubiquitinated protein aggregates via its UBA domain and sequesters them into inclusion bodies via its PB1 domain. SQSTM1also interacts with phagophores via its LC3-interacting (LIR) motif. However, a regulatory mechanism for autophagic receptors is not yet understood...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812082/a-broader-view-on-ion-heating-in-traveling-wave-devices-using-fragmentation-of-csi-clusters-and-extent-of-h%C3%AB-migration-as-molecular-thermometers
#6
Frederik Lermyte, Frank Sobott
Electron transfer dissociation (ETD) is becoming increasingly important in mass spectrometry-based analysis of peptides and proteins. Supplemental collisional activation of undissociated electron transfer products can significantly increase fragmentation yield and sequence coverage, but hydrogen rearrangements - specifically, transfer of a hydrogen radical from a c to a z fragment - lead to distorted isotope distributions and increased potential for signal overlap. Concomitant collisional activation during the ion/ion reaction significantly reduces these rearrangements, but, in ion traps, also leads to lower reaction rates and reduced overlap of anion and cation clouds...
August 16, 2017: Analyst
https://www.readbyqxmd.com/read/28810879/quantification-of-mutant-spop-proteins-in-prostate-cancer-using-mass-spectrometry-based-targeted-proteomics
#7
Hui Wang, Christopher E Barbieri, Jintang He, Yuqian Gao, Tujin Shi, Chaochao Wu, Athena A Schepmoes, Thomas L Fillmore, Sung-Suk Chae, Dennis Huang, Juan Miguel Mosquera, Wei-Jun Qian, Richard D Smith, Sudhir Srivastava, Jacob Kagan, David G Camp, Karin D Rodland, Mark A Rubin, Tao Liu
BACKGROUND: Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region with multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations...
August 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28810828/suitable-reference-gene-for-quantitative-real-time-pcr-analysis-of-gene-expression-in-gonadal-tissues-of-minnow-puntius-sophore-under-high-temperature-stress
#8
Arabinda Mahanty, Gopal Krishna Purohit, Sasmita Mohanty, Nihar Ranjan Nayak, Bimal Prasanna Mohanty
BACKGROUND: High ambient temperature is known to affect fish gonadal development and physiology in a variety of ways depending on the severity and duration of exposure; however, the underlying molecular mechanisms are poorly understood. Gonadal gene expression influence the gonadal development, physiology and the quality of egg/sperm produced in teleosts and the mechanistic understanding of spatio-temporal changes in the gonadal gene expression could be instrumental in controlling the fate of egg/sperm and the quality of seed produced...
August 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28810250/cerebral-small-vessel-disease-is-associated-with-dysregulation-in-the-ubiquitin-proteasome-system-and-other-major-cellular-pathways-in-specific-brain-regions
#9
Marie-Françoise Ritz, Caspar Grond-Ginsbach, Felix Fluri, Manja Kloss, Markus Tolnay, Nils Peters, Stefan Engelter, Philippe Lyrer
BACKGROUND/AIMS: Cerebral small vessel disease (SVD) is characterized by periventricular white matter (WM) changes and can lead to vascular dementia, the second most common form of age-dependent dementia. The pathogenesis of the disease remains poorly understood, and studies of its molecular basis are limited. By profiling gene expression of dissected postmortem brain tissue in SVD patients and comparisons with tissue of nonneurological controls, we aimed to identify genes and processes that are involved in the pathogenesis of SVD to gain new pathogenetic insights...
August 16, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28809541/ubiquitin-chains-modified-by-the-bacterial-ligase-sdea-are-protected-from-dub-hydrolysis
#10
Kedar Puvar, Yiyang Zhou, Jiazhang Qiu, Zhao-Qing Luo, Mary J Wirth, Chittaranjan Das
The SidE family of Legionella pneumophila effectors are a unique group of ubiquitin-modifying enzymes. Along with catalyzing NAD+-dependent ubiquitination of certain host proteins independent of the canonical E1/E2/E3 pathway, they have also been shown to produce phosphoribosylated free ubiquitin. This modified ubiquitin product is incompatible with conventional E1/E2/E3 ubiquitination processes, with the potential to lockdown various cellular functions that are dependent on ubiquitin signaling. Here, we show that in addition to free ubiquitin, Lys63, Lys48, Lys11 and Met1-linked diubiquitin chains are also modified by SdeA in a similar fashion...
August 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28809000/post-translational-modification-profiling-functional-proteomics-for-the-analysis-of-immune-regulation
#11
Avital Eisenberg-Lerner, Ifat Regev, Yifat Merbl
Posttranslational modifications (PTMs) of proteins are an integral part of major cellular regulatory mechanisms dictating protein function, localization, and stability. The capacity to screen PTMs using protein microarrays has advanced our ability to identify their targets and regulatory role. This chapter discusses a unique procedure that combines functional extract-based activity assay with large-scale screening utilities of protein microarrays. This "PTM-profiling" system offers advantages in quantitatively identifying modifications in an unbiased manner in the context of specific cellular conditions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808481/cul4b-is-a-novel-prognostic-marker-in-cholangiocarcinoma
#12
Pengyu Li, Lili Zhang, Muyi Yang, Mei Qi, Xing Jin, Bo Han
Cullin 4B (Cul4B), a scaffold protein that assembles the ubiquitin ligase complex, is involved in a wide variety of physiological and developmental processes, such as cell cycle progression, DNA damage response and gene expression regulation. Cul4B is overexpressed in various solid tumors. However, the prognostic value and role of Cul4B in cholangiocarcinoma (CCA) is largely unknown. The present study demonstrated that Cul4B was overexpressed in 21 (26.6%) of 79 patients with intrahepatic CCA, and in 40 (28...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28808415/foxo-signaling-pathways-as-therapeutic-targets-in-cancer
#13
REVIEW
Mohd Farhan, Haitao Wang, Uma Gaur, Peter J Little, Jiangping Xu, Wenhua Zheng
Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28808068/deletion-of-angiotensin-converting-enzyme-2-promotes-hypertensive-nephropathy-by-targeting-smad7-for-ubiquitin-degradation
#14
Zhen Liu, Xiao-Ru Huang, Hai-Yong Chen, Erik Fung, Jian Liu, Hui-Yao Lan
Angiotensin-converting enzyme-2 (ACE2) is downregulated in hypertensive nephropathy. The present study investigated the mechanisms whereby loss of ACE2 promoted angiotensin II-induced hypertensive nephropathy in ACE2 gene knockout mice. We found that compared with wild-type animals, mice lacking ACE2 developed much more severe hypertensive nephropathy in response to chronic angiotensin II infusion, including higher levels of blood pressure, urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation...
August 14, 2017: Hypertension
https://www.readbyqxmd.com/read/28808060/the-human-rna-binding-protein-and-e3-ligase-mex-3c-binds-the-mex-3-recognition-element-mre-motif-with-high-affinity
#15
Lingna Yang, Chongyuan Wang, Fudong Li, Jiahai Zhang, Anam Nayab, Jihui Wu, Yunyu Shi, Qingguo Gong
MEX-3 is a KH domain-containing RNA-binding protein, first identified as a translational repressor in Caenorhabditis elegans, while its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3' UTR and posttranscriptional regulation of MEX-3 target transcripts...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807996/klhl6-deficiency-impairs-transitional-b-cell-survival-and-differentiation
#16
Barbara Bertocci, Damiana Lecoeuche, Delphine Sterlin, Julius Kühn, Baptiste Gaillard, Annie De Smet, Frederique Lembo, Christine Bole-Feysot, Nicolas Cagnard, Tatiana Fadeev, Auriel Dahan, Jean-Claude Weill, Claude-Agnès Reynaud
Klhl6 belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. Several of these proteins function as adaptors of the Cullin3 E3 ubiquitin ligase complex. In this article, we report that Klhl6 deficiency induces, as previously described, a 2-fold reduction in mature B cells. However, we find that this deficit is centered on the inability of transitional type 1 B cells to survive and to progress toward the transitional type 2 B cell stage, whereas cells that have passed this step generate normal germinal centers (GCs) upon a T-dependent immune challenge...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28807830/usp5-promotes-tumorigenesis-and-progression-of-pancreatic-cancer-by-stabilizing-foxm1-protein
#17
Xin-Yan Li, Hai-Yun Wu, Xiao-Fang Mao, Li-Xin Jiang, Yong-Xiang Wang
Increased ubiquitin-specific protease 5 (USP5) has been associated with tumorigenesis of malignancy including glioblastoma, melanoma and hepatocellular carcinoma. However, the role of USP5 in tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) has not been studied yet. In this study, we demonstrated that USP5 was significantly upregulated in a panel of PDAC cell lines and correlated with FoxM1 protein expression. USP5 knockdown inhibited proliferation of PANC-1 and SW1990, two PDAC cell lines. In the mouse xenografted pancreatic tumor model, suppression of USP5 significantly decreased tumor growth, correlated with down regulation of FoxM1...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807824/flavan-3-ol-delays-the-progression-of-disuse-atrophy-induced-by-hindlimb-suspension-in-mice
#18
Mao Ito, Naoto Kudo, Yuji Miyake, Tatsuya Imai, Tomoki Unno, Yoko Yamashita, Yoshihisa Hirota, Hitoshi Ashida, Naomi Osakabe
Periods of skeletal muscle disuse, for example due to a sedentary lifestyle or bed rest, are associated with aging and can lead to muscle atrophy. We previously found that the flavan 3-ol fraction derived from cocoa (FL) enhanced energy expenditure with metabolic changes in skeletal muscle. In the present study, we examined the effect of FL on disuse muscle atrophy induced by hindlimb suspension in mice. Male C57BL/6J mice were assigned to four groups as follows: unsuspended-vehicle, unsuspended-FL, suspended-vehicle, and suspended-FL...
August 11, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28807725/the-rnf146-e3-ubiquitin-ligase-is-required-for-the-control-of-wnt-signaling-and-body-pattern-formation-in-xenopus
#19
Xuechen Zhu, Rui Xing, Renbo Tan, Rongyang Dai, Qinghua Tao
The RING finger protein Rnf146 encodes an E3 ubiquitin ligase capable of targeting poly-ADP-ribosylated substrates for proteasomal degradation. Rnf146 has been identified as a critical regulator of Axin1 and thus of Wnt/β-catenin signaling. However its physiological significance in vertebrate embryonic development remains to be demonstrated. In this study, we take advantages of early Xenopus embryos to demonstrate that Rnf146 is essential for embryonic pattern formation. Depletion of zygotic Rnf146 using a translation blocking morpholino oligo (MO) results in anteriorized development and increased expression the anterior marker gene Otx2, consistent the notion that Rnf146 is a positive regulator of Wnt/β-catenin signaling through negatively regulating Axin1 expression...
August 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28807601/ubx-domain-containing-proteins-are-involved-in-lipid-homeostasis-and-stress-responses-in-pichia-pastoris
#20
Meng Zhang, Qilin Yu, Zhe Liu, Chen Liang, Biao Zhang, Mingchun Li
Ubiquitin regulatory X (UBX) domain-containing proteins constitute a family of proteins and are substrate adaptors of AAA ATPase Cdc48. UBX proteins can bind to the N-terminal region of Cdc48 to perform endoplasmic reticulum associated protein degradation (ERAD). In this study, we identified two UBX domain-containing proteins, Ubx1 and Ubx2, in Pichia pastoris and found that the two proteins could recover the growth defect of Saccharomyces cerevisiae in ubx2Δ. Our results revealed that Ubx1 and Ubx2 play critical roles in synthesis of unsaturated fatty acids by affecting Spt23...
August 11, 2017: International Journal of Biochemistry & Cell Biology
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