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e3 ligase

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https://www.readbyqxmd.com/read/28821619/dsc-e3-ligase-localization-to-the-golgi-requires-the-atpase-cdc48-and-cofactor-ufd1-for-activation-of-sterol-regulatory-element-binding-protein-in-fission-yeast
#1
Risa Burr, Diedre Ribbens, Sumana Raychaudhuri, Emerson V Stewart, Jason Ho, Peter J Espenshade
Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases Associated with diverse cellular Activities (AAA+) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released in the cytosol to enter the nucleus and regulate gene expression...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28820178/erratum-e3-ubiquitin-ligase-znrf4-negatively-regulates-nod2-signalling-and-induces-tolerance-to-mdp
#2
Pradeep Bist, Wan Shoo Cheong, Aylwin Ng, Neha Dikshit, Bae Hoon Kim, Niyas Kudukkil Pulloor, Hanif Javanmard Khameneh, Matija Hedl, Avinash R Shenoy, Vanniarajan Balamuralidhar, Najib Bin Abdul Malik, Michelle Hong, Albert Neutzner, Keh-Chuang Chin, Koichi S Kobayashi, Antonio Bertoletti, Alessandra Mortellaro, Clara Abraham, John D MacMicking, Ramnik J Xavier, Bindu Sukumaran
This corrects the article DOI: 10.1038/ncomms15865.
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819320/genome-wide-identification-and-expression-analysis-of-e2-ubiquitin-conjugating-enzymes-in-tomato
#3
Bhaskar Sharma, Tarun Kumar Bhatt
The ubiquitin-proteasomal degradation mechanism has gained the attention over the past decade. The E2 ubiquitin conjugating enzymes are the crucial part of ubiquitination mechanism and they are believed to hold imperative association for plant development. It accepts ubiquitin from the E1 enzyme and interacts with the E3 ligase to transfer ubiquitin or directly transfers ubiquitin to the substrate. The functional aspects of E2 ubiquitin enzymes in plant systems are unclear. Tomato is being used as a model plant and rarely explored to study E2 ubiquitin enzyme...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818379/influence-of-tagw2-6a-on-seed-development-in-wheat-by-negatively-regulating-gibberellin-synthesis
#4
Qingyan Li, Liqun Li, Yan Liu, Qian Lv, Heng Zhang, Jian Zhu, Xuejun Li
Gibberellins (GA) are involved in seed development and E3 ubiquitin-ligases actively participate in GA perception and signal transduction. TaGW2-6A encodes a RING E3 ubiquitin-ligase that negatively regulates grain size. Therefore, Chinese Spring (CS) and its TaGW2-6A allelic variants (NIL31) were investigated to elucidate the relative contribution of GA to the regulation of seed development in wheat. The expression levels of GA biosynthesis and response genes were higher in NIL31 than CS, especially those of GA 3-oxidase and GASA4...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28818370/overexpression-of-vpeifp1-a-novel-f-box-kelch-repeat-protein-from-wild-chinese-vitis-pseudoreticulata-confers-higher-tolerance-to-powdery-mildew-by-inducing-thioredoxin-z-proteolysis
#5
Jie Wang, Wenkong Yao, Lei Wang, Fuli Ma, Weihuo Tong, Chen Wang, Rui Bao, Changyue Jiang, Yazhou Yang, Jianxia Zhang, Yan Xu, Xiping Wang, Chaohong Zhang, Yuejin Wang
An F-box protein (VpEIFP1) induced by Erysiphe necator was isolated from Vitis pseudoreticulata, a wild Chinese grapevine species naturally resistant to powdery mildew (PM). It contains an F-box domain and two Kelch-repeat motifs. Expression profiles indicate the VpEIFP1 is strongly induced at both transcriptional and translational levels by PM infection. A subcellular localisation assay showed that VpEIFP1 is predominantly located in the nucleus and cytoplasm. Overexpression of VpEIFP1 accelerated the accumulation of hydrogen peroxide (H2O2) and up-regulated the expressions of ICS2, NPR1 and PR1 involved in defence responses, resulting in suppression of PM germination and growth...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28817834/mdm2-promotes-epithelial-mesenchymal-transition-and-metastasis-of-ovarian-cancer-skov3-cells
#6
Ying Chen, Dan-Dan Wang, Ye-Ping Wu, Dan Su, Tian-Yi Zhou, Ren-Hua Gai, Ying-Ying Fu, Lin Zheng, Qiao-Jun He, Hong Zhu, Bo Yang
BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated...
August 17, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28816574/sgt1-hsp90-complex-is-required-for-cenp-a-deposition-at-centromeres
#7
Yohei Niikura, Risa Kitagawa, Hiroo Ogi, Katsumi Kitagawa
The centromere plays an essential role in accurate chromosome segregation, and defects in its function lead to aneuploidy and thus cancer. The centromere-specific histone H3 variant CENP-A is proposed to be the epigenetic mark of the centromere, as active centromeres require CENP-A-containing nucleosomes to direct the recruitment of multiple kinetochore proteins. CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. However, the mechanism that controls the E3 ligase activity of the CUL4A-RBX1-COPS8 complex remains obscure...
August 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28814529/selective-hif-1-regulation-under-nonhypoxic-conditions-by-the-p42-p44-map-kinase-inhibitor-pd184161
#8
Maroua Jalouli, Sophie Mokas, Catherine A Turgeon, Laurent Lamalice, Darren E Richard
Hypoxia-inducible factor-1 (HIF-1) is a key gene regulator for cellular adaptation to low oxygen. In addition to hypoxia, several nonhypoxic stimuli, including hormones and growth factors, are an essential part for cell-specific HIF-1 regulation. Our studies have highlighted angiotensin II (AngII), a vasoactive hormone, as a potent HIF-1 activator in vascular smooth muscle cells (VSMC). AngII increases HIF-1 transcriptional activity by modulating specific signaling pathways. In VSMC, p42/p44 mitogen-activated protein kinase (MAPK) pathway activation is essential for HIF-1-mediated transcription during AngII treatment...
August 16, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28813668/subnuclear-relocalization-of-structure-specific-endonucleases-in-response-to-dna-damage
#9
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/28811325/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#10
Luxi Chen, Yi Yuan, Shreya Kar, Madhu M Kanchi, Suruchi Arora, Ji E Kim, Pei F Koh, Einas Yousef, Ramar P Samy, Muthu K Shanmugam, Tuan Z Tan, Sung W Shin, Frank Arfuso, Han M Shen, Henry Yang, Boon C Goh, Joo I Park, Louis Gaboury, Peter E Lobie, Gautam Sethi, Lina Hk Lim, Alan P Kumar
Metastatic breast cancer is still remain incurable so far, new specifically targeted and more effective therapies for triple negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data has established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines which model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and Peroxisome Proliferator-Activated Receptor gamma (PPARγ)...
August 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28810879/quantification-of-mutant-spop-proteins-in-prostate-cancer-using-mass-spectrometry-based-targeted-proteomics
#11
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/28809541/ubiquitin-chains-modified-by-the-bacterial-ligase-sdea-are-protected-from-deubiquitinase-hydrolysis
#12
Kedar Puvar, Yiyang Zhou, Jiazhang Qiu, Zhao-Qing Luo, Mary J Wirth, Chittaranjan Das
The SidE family of Legionella pneumophila effectors is 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 lock down 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 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28808068/deletion-of-angiotensin-converting-enzyme-2-promotes-hypertensive-nephropathy-by-targeting-smad7-for-ubiquitin-degradation
#13
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
#14
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
#15
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/28807725/the-rnf146-e3-ubiquitin-ligase-is-required-for-the-control-of-wnt-signaling-and-body-pattern-formation-in-xenopus
#16
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/28807436/simple-and-efficient-knockdown-of-his-tagged-proteins-by-ternary-molecules-consisting-of-a-his-tag-ligand-a-ubiquitin-ligase-ligand-and-a-cell-penetrating-peptide
#17
Takayuki Hattori, Koyo Okitsu, Norikazu Yamazaki, Nobumichi Ohoka, Norihito Shibata, Takashi Misawa, Masaaki Kurihara, Yosuke Demizu, Mikihiko Naito
We designed and synthesized hybrid molecules for a protein knockdown method based on the recognition of a His-tag fused to a protein of interest (POI). The synthesized target protein degradation inducers contained three functional moieties: a His-tag ligand (nickel nitrilotriacetic acid [Ni-NTA]), an E3 ligand (bestatin [BS] or MV1), and a carrier peptide (Tat or nonaarginine [R9]). The designed hybrid molecules, BS-Tat-Ni-NTA, MV1-Tat-Ni-NTA, BS-R9-Ni-NTA, and MV1-R9-Ni-NTA, efficiently degraded His-tagged cellular retinoic acid binding protein 2 via the ubiquitin-proteasome system (UPS)...
August 2, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#18
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28806172/mobilization-of-line-1-retrotransposons-is-restricted-by-tex19-1-in-mouse-embryonic-stem-cells
#19
Marie MacLennan, Marta García-Cañadas, Judith Reichmann, Elena Khazina, Gabriele Wagner, Christopher J Playfoot, Carmen Salvador-Palomeque, Abigail R Mann, Paula Peressini, Laura Sanchez, Karen Dobie, David Read, Chao-Chun Hung, Ragnhild Eskeland, Richard R Meehan, Oliver Weichenrieder, Jose Luis García-Pérez, Ian R Adams
Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization...
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28805822/intrinsic-bet-inhibitor-resistance-in-spop-mutated-prostate-cancer-is-mediated-by-bet-protein-stabilization-and-akt-mtorc1-activation
#20
Pingzhao Zhang, Dejie Wang, Yu Zhao, Shancheng Ren, Kun Gao, Zhenqing Ye, Shangqian Wang, Chun-Wu Pan, Yasheng Zhu, Yuqian Yan, Yinhui Yang, Di Wu, Yundong He, Jun Zhang, Daru Lu, Xiuping Liu, Long Yu, Shimin Zhao, Yao Li, Dong Lin, Yuzhuo Wang, Liguo Wang, Yu Chen, Yinghao Sun, Chenji Wang, Haojie Huang
Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anticancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is the most frequently mutated in primary prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them. In contrast, prostate cancer-associated SPOP mutants show impaired binding to BET proteins, resulting in decreased proteasomal degradation and accumulation of these proteins in prostate cancer cell lines and patient specimens and causing resistance to BET inhibitors...
August 14, 2017: Nature Medicine
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