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https://www.readbyqxmd.com/read/29145196/aqp2-abundance-is-regulated-by-the-e3-ligase-chip-via-hsp70
#1
Mariangela Centrone, Marianna Ranieri, Annarita Di Mise, Sante Princiero Berlingerio, Annamaria Russo, Peter M T Deen, Olivier Staub, Giovanna Valenti, Grazia Tamma
BACKGROUND/AIMS: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. METHODS: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting...
November 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29144457/a-ubiquitin-dependent-signalling-axis-specific-for-alkbh-mediated-dna-dealkylation-repair
#2
Joshua R Brickner, Jennifer M Soll, Patrick M Lombardi, Cathrine B Vågbø, Miranda C Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E Sullender, Elyse Blazosky, Andrea K Byrum, Yu Zhao, Mark A Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger, Nima Mosammaparast
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144391/antimicrobial-peptide-epinecidin-1-modulates-myd88-protein-levels-via-the-proteasome-degradation-pathway
#3
Bor-Chyuan Su, Jyh-Yih Chen
The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
November 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29142217/fbxo32-promotes-microenvironment-underlying-epithelial-mesenchymal-transition-via-ctbp1-during-tumour-metastasis-and-brain-development
#4
Sanjeeb Kumar Sahu, Neha Tiwari, Abhijeet Pataskar, Yuan Zhuang, Marina Borisova, Mustafa Diken, Susanne Strand, Petra Beli, Vijay K Tiwari
The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142209/fbxo4-mediated-degradation-of-fxr1-suppresses-tumorigenesis-in-head-and-neck-squamous-cell-carcinoma
#5
Shuo Qie, Mrinmoyee Majumder, Katarzyna Mackiewicz, Breege V Howley, Yuri K Peterson, Philip H Howe, Viswanathan Palanisamy, J Alan Diehl
The Fbxo4 tumour suppressor is a component of an Skp1-Cul1-F-box E3 ligase for which two substrates are known. Here we show purification of SCF(Fbxo4) complexes results in the identification of fragile X protein family (FMRP, Fxr1 and Fxr2) as binding partners. Biochemical and functional analyses reveal that Fxr1 is a direct substrate of SCF(Fbxo4). Consistent with a substrate relationship, Fxr1 is overexpressed in Fbxo4 knockout cells, tissues and in human cancer cells, harbouring inactivating Fbxo4 mutations...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142135/autographa-californica-nucleopolyhedrovirus-ac141-exon0-a-potential-e3-ubiquitin-ligase-interacts-with-viral-ubiquitin-and-ac66-to-facilitate-nucleocapsid-egress
#6
Siddhartha Biswas, Leslie G Willis, Minggang Fang, Yingchao Nie, David A Theilmann
During the infection cycle of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) two forms of virions are produced, budded virus (BV) and occlusion derived virus (ODV). Nucleocapsids that form BV have to egress from the nucleus whereas nucleocapsids that form ODVs remain inside the nucleus. The molecular mechanism that determines whether nucleocapsids remain inside or egress from the nucleus is unknown. AC141 (a predicted E3 ubiquitin ligase) and viral ubiquitin (vUbi) have both been shown to be required for efficient BV production...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142133/human-adenovirus-infection-causes-the-cellular-mkrn1-e3-ubiquitin-ligase-degradation-involving-the-viral-core-protein-pvii
#7
Raviteja Inturi, Kwangchol Mun, Katrin Singethan, Sabrina Schreiner, Tanel Punga
Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII interacting protein in HAdV-C5-infected cells...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29139123/new-insights-into-the-mechanisms-of-phytochrome-cryptochrome-coaction
#8
REVIEW
Qin Wang, Qing Liu, Xu Wang, Zecheng Zuo, Yoshito Oka, Chentao Lin
Contents I. II. III. IV. SUMMARY: Plants perceive and respond to light signals by multiple sensory photoreceptors, including phytochromes and cryptochromes, which absorb different wavelengths of light to regulate genome expression and plant development. Photophysiological analyses have long revealed the coordinated actions of different photoreceptors, a phenomenon referred to as the photoreceptor coaction. The mechanistic explanations of photoreceptor coactions are not fully understood...
November 15, 2017: New Phytologist
https://www.readbyqxmd.com/read/29138676/resveratrol-modulation-of-protein-expression-in-parkin-mutant-human-skin-fibroblasts-a-proteomic-approach
#9
Daniele Vergara, Antonio Gaballo, Anna Signorile, Anna Ferretta, Paola Tanzarella, Consiglia Pacelli, Marco Di Paola, Tiziana Cocco, Michele Maffia
In this study, we investigated by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) analysis the effects of resveratrol treatment on skin primary fibroblasts from a healthy subject and from a parkin-mutant early onset Parkinson's disease patient. Parkin, an E3 ubiquitin ligase, is the most frequently mutated gene in hereditary Parkinson's disease. Functional alteration of parkin leads to impairment of the ubiquitin-proteasome system, resulting in the accumulation of misfolded or aggregated proteins accountable for the neurodegenerative process...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29138408/both-nodal-signalling-and-stochasticity-select-for-prospective-distal-visceral-endoderm-in-mouse-embryos
#10
Katsuyoshi Takaoka, Hiromi Nishimura, Hiroshi Hamada
Anterior-posterior (A-P) polarity of mouse embryos is established by distal visceral endoderm (DVE) at embryonic day (E) 5.5. Lefty1 is expressed first at E3.5 in a subset of epiblast progenitor cells (L1(epi) cells) and then in a subset of primitive endoderm cells (L1(dve) cells) fated to become DVE. Here we studied how prospective DVE cells are selected. Lefty1 expression in L1(epi) and L1(dve) cells depends on Nodal signaling. A cell that experiences the highest level of Nodal signaling begins to express Lefty1 and becomes an L1(epi) cell...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29138248/usp1-uaf1-deubiquitinase-complex-stabilizes-tbk1-and-enhances-antiviral-responses
#11
Zhongxia Yu, Hui Song, Mutian Jia, Jintao Zhang, Wenwen Wang, Qi Li, Lining Zhang, Wei Zhao
Optimal activation of TANK-binding kinase 1 (TBK1) is crucial for initiation of innate antiviral immunity and maintenance of immune homeostasis. Although several E3 ubiquitin ligases have been reported to regulate TBK1 activation by mediating its polyubiquitination, the functions of deubiquitinase on TBK1 activity remain largely unclear. Here, we identified a deubiquitinase complex, which is formed by ubiquitin specific peptidase 1 (USP1) and USP1-associated factor 1 (UAF1), as a viral infection-induced physiological enhancer of TBK1 expression...
November 14, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29138008/g-quadruplex-structure-at-intron-2-of-tfe3-and-its-role-in-xp11-2-translocation-and-splicing
#12
Shiv Prakash Verma, Parimal Das
Transcription Factor E3 (TFE3) translocation is found in a group of different type of cancers and most of the translocations are located in the 5' region of TFE3 which may be considered as Breakpoint Region (BR). In our In silico study by QGRS mapper and non BdB web servers we found a Potential G-quadruplex forming Sequence (PQS) in the intron 2 of TFE3 gene. In vitro G-quadruplex formation was shown by native PAGE in presence of Pyridostatin(PDS), which with inter molecular secondary structure caused reduced mobility to migrate slower...
November 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29137327/regulation-of-fbxo4-mediated-icam-1-protein-stability-in-metastatic-breast-cancer
#13
Jae-Hyeok Kang, Mi-Young Choi, Yan-Hong Cui, Neha Kaushik, Nizam Uddin, Ki-Chun Yoo, Min-Jung Kim, Su-Jae Lee
Advanced or progressive cancers share common traits such as altered transcriptional modulation, genetic modification, and abnormal post-translational regulation. These processes influence protein stability and cellular activity. Intercellular adhesion molecule-1 (ICAM-1) is involved in the malignant progression of various human cancers, including breast, liver, renal, and pancreatic cancers, but protein stability has not been deal with in metastatic breast cancer. Additionally, the relevance of the stability maintenance of ICAM-1 protein remains obscure...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137325/rlim-suppresses-hepatocellular-carcinogenesis-by-up-regulating-p15-and-p21
#14
Yongsheng Huang, Meng Nie, Chuang Li, Yingjie Zhao, Jiahui Li, Lan Zhou, Lin Wang
Hepatocellular carcinogenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation and apoptosis. p15 and p21 are cyclin-dependent kinase inhibitors, which arrest cell proliferation and serve as critical tumor suppressors. Here we report that the E3 ubiquitin ligase RLIM expression is downregulated in hepatocellular carcinoma patients, and correlated with p15 and p21 expression in clinical progression. In addition, we showed that RLIM overexpression suppresses the cell growth and arrests cell cycle progression of hepatocellular carcinoma...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136849/simultaneous-determination-of-three-estrogens-in-human-saliva-without-derivatization-or-liquid-liquid-extraction-for-routine-testing-via-miniaturized-solid-phase-extraction-with-lc-ms-ms-detection
#15
Xiaoguang Sunny Li, Shu Li, Gottfried Kellermann
Accurate quantitation of estrogens (i.e, estrone (E1), estradiol (E2) and estriol (E3)) is valuable for clinical assessment of human health and disease. Alterations in estrogen levels have been implicated in numerous pathological conditions. However, inadequacies in sensitivity and specificity, cumbersome sample preparation and invasive specimen collection hamper the usability of available methods for clinical applications. Herein, a simple, rapid, highly sensitive and specific LC-MS/MS method was developed and validated for the simultaneous determination of three estrogens in human saliva providing a non-invasive alternative to conventional blood samples...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29133641/simultaneous-use-of-amniotic-membrane-and-mitomycin-c-in-trabeculectomy-for-primary-glaucoma
#16
Usha Yadava, Kirti Jaisingh, Sonal Dangda, Prolima Thacker, Kirti Singh, Yashpal Goel
PURPOSE: This study aimed to propose the role of amniotic membrane transplantation (AMT) as an additional modulator in primary Mitomycin C (MMC)-augmented trabeculectomy. METHODS: This was a randomized prospective interventional study. Forty eyes of 39 adult patients with uncontrolled primary glaucoma were randomly divided into two equal groups. Control group underwent trabeculectomy augmented with MMC while the study group underwent additional AMT. Patients were followed up for 12 months and outcomes measured were intraocular pressure (IOP), need for additional intervention, and bleb morphology...
November 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29132012/distinct-ezrin-truncations-differentiate-metastases-in-sentinel-lymph-nodes-from-unaffected-lymph-node-tissues-from-primary-breast-tumors-and-from-healthy-glandular-breast-tissues
#17
Claudia Röwer, Christian George, Toralf Reimer, Bernd Stengel, Anngret Radtke, Bernd Gerber, Michael O Glocker
BACKGROUND: Lymph node metastasis status is a prognostic factor for further lymph node involvement and for patient survival in breast cancer patients. Frozen section analysis of lymph nodes is a reliable method for detection of macro-metastases. However, this method is far less effective in detecting micro-metastases, requesting improved diagnostic procedures. METHODS: We investigated expression and truncation of ezrin in (i) sentinel lymph node metastases, (ii) unaffected axillary lymph nodes, (iii) primary breast tumors, and (iv) healthy glandular breast tissues using 2D gel electrophoresis, SDS-PAGE, and mass spectrometry in addition to Western blotting...
November 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29129718/lessons-in-protac-design-from-selective-degradation-with-a-promiscuous-warhead
#18
Daniel P Bondeson, Blake E Smith, George M Burslem, Alexandru D Buhimschi, John Hines, Saul Jaime-Figueroa, Jing Wang, Brian D Hamman, Alexey Ishchenko, Craig M Crews
Inhibiting protein function selectively is a major goal of modern drug discovery. Here, we report a previously understudied benefit of small molecule proteolysis-targeting chimeras (PROTACs) that recruit E3 ubiquitin ligases to target proteins for their ubiquitination and subsequent proteasome-mediated degradation. Using promiscuous CRBN- and VHL-recruiting PROTACs that bind >50 kinases, we show that only a subset of bound targets is degraded. The basis of this selectivity relies on protein-protein interactions between the E3 ubiquitin ligase and the target protein, as illustrated by engaged proteins that are not degraded as a result of unstable ternary complexes with PROTAC-recruited E3 ligases...
October 31, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29129717/a-chemoproteomic-approach-to-query-the-degradable-kinome-using-a-multi-kinase-degrader
#19
Hai-Tsang Huang, Dennis Dobrovolsky, Joshiawa Paulk, Guang Yang, Ellen L Weisberg, Zainab M Doctor, Dennis L Buckley, Joong-Heui Cho, Eunhwa Ko, Jaebong Jang, Kun Shi, Hwan Geun Choi, James D Griffin, Ying Li, Steven P Treon, Eric S Fischer, James E Bradner, Li Tan, Nathanael S Gray
Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted protein degradation represent an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK, and nine members of the CDK family, as degradable...
November 7, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29129716/the-advantages-of-targeted-protein-degradation-over-inhibition-an-rtk-case-study
#20
George M Burslem, Blake E Smith, Ashton C Lai, Saul Jaime-Figueroa, Daniel C McQuaid, Daniel P Bondeson, Momar Toure, Hanqing Dong, Yimin Qian, Jing Wang, Andrew P Crew, John Hines, Craig M Crews
Proteolysis targeting chimera (PROTAC) technology has emerged over the last two decades as a powerful tool for targeted degradation of endogenous proteins. Herein we describe the development of PROTACs for receptor tyrosine kinases, a protein family yet to be targeted for induced protein degradation. The use of VHL-recruiting PROTACs against this protein family reveals several advantages of degradation over inhibition alone: direct comparisons of fully functional, target-degrading PROTACs with target-inhibiting variants that contain an inactivated E3 ligase-recruiting ligand show that degradation leads to more potent inhibition of cell proliferation and a more durable and sustained downstream signaling response, and thus addresses the kinome rewiring challenge seen with many receptor tyrosine kinase inhibitors...
October 25, 2017: Cell Chemical Biology
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