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Ji Cheng, Jianping Guo, Zhiwei Wang, Brian J North, Kaixiong Tao, Xiangpeng Dai, Wenyi Wei
Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner...
November 8, 2017: Biochimica et Biophysica Acta
Kwami F Ketosugbo, Henry L Bushnell, Ruth I Johnson
Ubiquitination is a crucial post-translational modification that can target proteins for degradation. The E3 ubiquitin ligases are responsible for recognizing substrate proteins for ubiquitination, hence providing specificity to the process of protein degradation. Here, we describe a genetic modifier screen that identified E3 ligases that modified the rough-eye phenotype generated by expression of cindrRNAi transgenes during Drosophila eye development. In total, we identified 36 E3 ligases, as well as 4 Cullins, that modified the mild cindrRNA mis-patterning phenotype...
2017: PloS One
Alhejandra Álvarez, Felipe Uribe, Jimena Canales, Cristóbal Romero, Andrea Soza, María A Peña, Marcelo Antonelli, Oscar Almarza, Oscar Cerda, Héctor Toledo
In order to establish infection, bacterial pathogens modulate host cellular processes by using virulence factors, which are delivered from the bacteria to the host cell leading to cellular reprogramming. In this context, several pathogens regulate the ubiquitin proteasome system in order to regulate the cellular effectors required for their successful colonization and persistance. In this study, we investigated how Helicobacter pylori affect the ubiquitination of the host proteins to achieve the adherence to the cells, using AGS gastric epithelial cells cultured with H...
2017: Frontiers in Cellular and Infection Microbiology
M Qi, M Jiao, X Li, J Hu, L Wang, Y Zou, M Zhao, R Zhang, H Liu, J Mi, L Zhang, L Liu, Y Gong, B Han
Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. However, its clinical significance and underlying molecular mechanisms in gastric cancer (GC) remain largely unknown. In this study, we found that CUL4B was significantly overexpressed in GC tissues and its overexpression was correlated with lymph node metastasis and poor prognosis. Through gain- and loss-of-function experiments, we showed that CUL4B promotes GC cell invasion and epithelial-mesenchymal transition (EMT) in vitro, as well as tumor growth and metastasis in vivo...
November 6, 2017: Oncogene
Kirthi C Reddy, Tal Dror, Jessica N Sowa, Johan Panek, Kevin Chen, Efrem S Lim, David Wang, Emily R Troemel
Maintenance of protein homeostasis, or proteostasis, is crucial for organismal health. Disruption of proteostasis can lead to the accumulation of protein aggregates, which are associated with aging and many human diseases such as Alzheimer's disease [1-3]. Through analysis of the C. elegans host response to intracellular infection, we describe here a novel response pathway that enhances proteostasis capacity and appears to act in parallel to well-studied proteostasis pathways. These findings are based on analysis of the transcriptional response to infection by the intracellular pathogen Nematocida parisii [4]...
October 30, 2017: Current Biology: CB
Justin M Reitsma, Xing Liu, Kurt M Reichermeier, Annie Moradian, Michael J Sweredoski, Sonja Hess, Raymond J Deshaies
SCF (Skp1-Cullin-F-box) ubiquitin ligases comprise several dozen modular enzymes that have diverse roles in biological regulation. SCF enzymes share a common catalytic core containing Cul1⋅Rbx1, which is directed toward different substrates by a variable substrate receptor (SR) module comprising 1 of 69 F-box proteins bound to Skp1. Despite the broad cellular impact of SCF enzymes, important questions remain about the architecture and regulation of the SCF repertoire, including whether SRs compete for Cul1 and, if so, how this competition is managed...
October 26, 2017: Cell
Holly Robertson, John D Hayes, Calum Sutherland
Glycogen Synthase Kinase-3 (GSK3) was originally reported as a key enzyme of glucose homeostasis through regulation of the rate of glycogen synthesis. It has subsequently been found to influence most cellular processes, including growth, differentiation and death, as part of its role in modulating response to hormonal, nutritional and cellular stress stimuli. More than 100 protein targets for GSK3 have been proposed although only a small fraction of these have been convincingly validated in physiological cell systems...
November 1, 2017: Biochemical Pharmacology
Xia-Wa Mao, Jia-Quan Xiao, Gang Xu, Zhong-Yi Li, Hui-Feng Wu, Yi Li, Yi-Chun Zheng, Nan Zhang
Increased expression of cullin 4B (CUL4B) is linked to progression in several cancers. This study aims to explore the effects of CUL4B on bladder cancer (BC) metastasis and epithelial-to-mesenchymal transition (EMT) and potential correlation to the Wnt/β-catenin signaling pathway. We collected BC tissues and adjacent normal tissues from 124 BC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were employed in order to detect the expression of Wnt/β-catenin signaling pathway-related proteins and EMT markers...
September 29, 2017: Oncotarget
Marc A J Morgan, Ryan A Rickels, Clayton K Collings, Xiaolin He, Kaixiang Cao, Hans-Martin Herz, Kira A Cozzolino, Nebiyu A Abshiru, Stacy A Marshall, Emily J Rendleman, Christie C Sze, Andrea Piunti, Neil L Kelleher, Jeffrey N Savas, Ali Shilatifard
Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4-RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain...
October 1, 2017: Genes & Development
Xingqun Cheng, Sylvio Redanz, Nyssa Cullin, Xuedong Zhou, Xin Xu, Vrushali Joshi, Dipankar Koley, Justin Merritt, Jens Kreth
Commensal Streptococcus sanguinis and Streptococcus gordonii are pioneer oral biofilm colonizers. Characteristic for both is the SpxB-dependent production of H2O2, which is crucial for inhibiting competing biofilm members, especially the cariogenic species Streptococcus mutans H2O2 production is strongly impacted by environmental conditions, yet few mechanisms are known. Dental plaque pH is one of the key parameters dictating dental plaque ecology, and ultimately oral health status. Therefore, the objective of the current study was to characterize the effect of environmental pH upon H2O2 production by S...
October 27, 2017: Applied and Environmental Microbiology
Z-H Zhang, J Li, F Luo, Y-S Wang
OBJECTIVE:   SCCRO/DCUN1D1/DCN1 (squamous cell carcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin neddylation) is considered as an oncogene, but its role in the prostate cancer (PC) is still not clear. The current study aims to investigate the expression of SCCRO in PC tumor tissues, further its clinical significance, and proliferation inhibiting effect on PC cells in vitro. PATIENTS AND METHODS: RT-PCR was used to detect the expression of SCCRO in PC tissue and corresponding adjacent normal tissues from 160 cases, and its relationship with clinical pathological characteristics was analyzed...
October 2017: European Review for Medical and Pharmacological Sciences
Xun Tang, Ning Zhang, Huaijun Si, Alejandro Calderón-Urrea
BACKGROUND: Real-time quantitative PCR (RT-qPCR) is the most commonly used method for accurately detecting gene expression patterns. As part of RT-qPCR analysis, normalization of the data requires internal control gene(s) that display uniform expression under different biological conditions. However, no invariable internal control gene exists, and therefore more than one reference gene is needed to normalize RT-qPCR results. Identification of stable reference genes in potato will improve assay accuracy for selecting stress-tolerance genes and identifying molecular mechanisms conferring stress tolerance in this species...
2017: Plant Methods
Haibin Zhou, Jianfeng Lu, Liu Liu, Denzil Bernard, Chao-Yie Yang, Ester Fernandez-Salas, Krishnapriya Chinnaswamy, Stephanie Layton, Jeanne Stuckey, Qing Yu, Weihua Zhou, Zhenqiang Pan, Yi Sun, Shaomeng Wang
The Cullin-RING E3 ubiquitin ligases (CRLs) regulate homeostasis of ~20% of cellular proteins and their activation require neddylation of their cullin subunit. Cullin neddylation is modulated by a scaffolding DCN protein through interactions with both the cullin protein and an E2 enzyme such as UBC12. Here we report the development of DI-591 as a high-affinity, cell-permeable small-molecule inhibitor of the DCN1-UBC12 interaction. DI-591 binds to purified recombinant human DCN1 and DCN2 proteins with K i values of 10-12 nM, and disrupts the DCN1-UBC12 interaction in cells...
October 27, 2017: Nature Communications
Fangfang Chen, Chunxiao Zhang, Haonan Wu, Yue Ma, Xiaomin Luo, Xinqi Gong, Fan Jiang, Yaoting Gui, Hui Zhang, Fei Lu
Molecular oscillators are important cellular regulators of, for example, circadian clocks, oscillations of immune regulators, and short-period (ultradian) rhythms during embryonic development. The Notch signaling factor hairy and enhancer of split 1 (HES1) is a well-known repressor of proneural genes, and HES1 ultradian oscillation is essential for keeping cells in an efficiently proliferating progenitor state. HES1 oscillation is driven by both transcriptional self-repression and ubiquitin-dependent proteolysis...
October 25, 2017: Journal of Biological Chemistry
Masashi Maekawa, Kazufumi Tanigawa, Tomohisa Sakaue, Hiromi Hiyoshi, Eiji Kubota, Takashi Joh, Yuji Watanabe, Tomohiko Taguchi, Shigeki Higashiyama
Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is related to numerous pathophysiological events. We previously reported that a RING ubiquitin ligase complex scaffold protein, cullin-3 (CUL3), and one of its adaptor proteins, BAZF, regulated angiogenesis in the mouse retina by suppressing Notch signaling. However, the degree of inhibition of angiogenesis was made greater by CUL3 depletion than by BAZF depletion, suggesting other roles of CUL3 in angiogenesis besides the regulation of Notch signaling...
October 16, 2017: Biology Open
Jaehyun Kim, Fuminori Tsuruta, Tomomi Okajima, Sarasa Yano, Ban Sato, Tomoki Chiba
Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. Recent studies have revealed that mutations in klhl7 gene cause several disorders, such as retinitis pigmentosa (RP). Although KLHL7 is considered to be crucial for regulating the protein homeostasis, little is known about its biological functions. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity. TUT1 is normally localized in nucleolus; however, expression of KLHL7 facilitates a vulnerability of nucleolar integrity, followed by a decrease of TUT1 localization in nucleolus...
October 12, 2017: Biochemical and Biophysical Research Communications
Nyssa Cullin, Sylvio Redanz, Kirsten J Lampi, Justin Merritt, Jens Kreth
The overall health of the oral cavity is dependent upon a proper homeostasis between health-associated bacterial colonizers and bacteria known to promote dental caries. Streptococcus sanguinis is a health-associated commensal, a known early colonizer of the acquired tooth pellicle, and is naturally competent. We have shown that LytF, a competence-controlled murein hydrolase, is capable of inducing the release of extracellular DNA (eDNA) from oral bacteria. Precipitated and purified LytF were used as treatments against planktonic cultures and biofilms...
October 6, 2017: Applied and Environmental Microbiology
Tomohisa Sakaue, Masashi Maekawa, Hironao Nakayama, Shigeki Higashiyama
Tissue remodelling and regeneration in various pathophysiological conditions (e.g. the processes of development, pregnancy, inflammation, wound healing, tissue regeneration, tumor growth, etc.) require angiogenesis, a dynamically coordinated response to stimuli from the extracellular microenvironment. During angiogenic and angiostatic responses, endothelial cells play a central role in the blood vessel formation and regression. Angiostatic responses, which are evoked by crucial factors such as VEGF and DLL4, have been elucidated...
October 1, 2017: Journal of Biochemistry
Chunpeng An, Lin Li, Qingzhe Zhai, Yanrong You, Lei Deng, Fangming Wu, Rong Chen, Hongling Jiang, Hang Wang, Qian Chen, Chuanyou Li
Jasmonoyl-isoleucine (JA-Ile), the active form of the plant hormone jasmonate (JA), is sensed by the F-box protein CORONATINE INSENSITIVE 1 (COI1), a component of a functional Skp-Cullin-F-box E3 ubiquitin ligase complex. Sensing of JA-Ile by COI1 rapidly triggers genome-wide transcriptional changes that are largely regulated by the basic helix-loop-helix transcription factor MYC2. However, it remains unclear how the JA-Ile receptor protein COI1 relays hormone-specific regulatory signals to the RNA polymerase II general transcriptional machinery...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
Mark Bennett, Shin-Lin Tu, Chris Upton, Cassie McArtor, Amber Gillett, Tanya Laird, Mark O'Dea
Poxviruses have previously been detected in macropods with cutaneous papillomatous lesions, however to date, no comprehensive analysis of a poxvirus from kangaroos has been performed. Here we report the genome sequences of a western grey kangaroo poxvirus (WKPV) and an eastern grey kangaroo poxvirus (EKPV), named for the host species from which they were isolated, western grey (Macropus fuliginosus) and eastern grey (Macropus giganteus) kangaroos. Poxvirus DNA from WKPV and EKPV was isolated and entire coding genome regions determined through Roche GS Junior and Illumina Miseq sequencing, respectively...
September 27, 2017: Virus Research
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