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https://www.readbyqxmd.com/read/28733455/e3-ubiquitin-ligase-nedd4-induces-endocytosis-and-lysosomal-sorting-of-connexin43-to-promote-loss-of-gap-junctions
#1
Max Z Totland, Christian H Bergsland, Tone A Fykerud, Lars M Knudsen, Nikoline L Rasmussen, Peter W Eide, Zeremariam Yohannes, Vigdis Sørensen, Andreas Brech, Ragnhild A Lothe, Edward Leithe
Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin43 is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Connexin43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of connexin43 in cancer cells has remained elusive...
July 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28733427/biallelic-germline-mutations-in-rfwd3-may-induce-fanconi-anemia
#2
(no author information available yet)
The E3 ubiquitin ligase RFWD3 is mutated in a patient with Fanconi anemia lacking known Fanconi mutations.
July 21, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28731194/smurf1-promotes-the-proliferation-migration-and-invasion-of-gastric-cancer-cells
#3
Youmao Tao, Caixia Sun, Tao Zhang, Yan Song
Smad ubiquitin regulatory factor 1 (SMURF1), a well-known E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Accumulating studies have shown that SMURF1 acts as an oncogenic factor in human malignancies. However, the clinical significance of SMURF1 and its role in gastric cancer (GC) remain unclear. The expression of SMURF1 was detected in 68 cases of GC and corresponding tumor-adjacent specimens. Our results revealed that SMURF1 was prominently overexpressed in GC specimens compared to corresponding tumor-adjacent tissues...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731191/carboxy-terminus-hsc70-interacting-protein-exerts-a-tumor-inhibition-function-in-head-and-neck-cancer
#4
Meng Xiao, Ming Yan, Jianjun Zhang, Qin Xu, Wantao Chen
Several independent studies have reported the roles of the E3 ubiquitin ligase, carboxy-terminus Hsc70 interacting protein (CHIP) in various types of cancers. However, the biological effects of CHIP vary in regards to different cancers, and the role of CHIP in head and neck cancers (HNCs) remains unknown. In the present study, CHIP overexpression plasmids and CHIP knockdown lentivirus were constructed to affect the expression levels of CHIP protein and biological behaviors in HNC cell lines bilaterally. The biological behaviors regulated by CHIP in HNCs were investigated both in vivo and in vitro with a series of assays and analyses...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28730334/mir-181a-2-downregulates-the-e3-ubiquitin-ligase-cul4a-transcript-and-promotes-cell-proliferation
#5
Venkateshwarlu Bandi, Sudhakar Baluchamy
MiR-181a-2 plays a major role in cell proliferation both positively and negatively depending on tissue type by targeting several regulators 3'UTR regions. We have predicted several targets for miR-181a-2 through computational approaches and characterized one its interesting target, CUL4A, an E3 ubiquitin ligase. CUL4A regulates diverse functions in the cells including DNA repair, DNA replication, cell cycle, genomic stability through polyubiquitination of target proteins. Deregulation of both miR-181a-2 and CUL4A are reported in many cancerous cells, but the functional link between them is unknown...
August 2017: Medical Oncology
https://www.readbyqxmd.com/read/28724963/midnolin-is-a-novel-regulator-of-parkin-expression-and-is-associated-with-parkinson-s-disease
#6
Yutaro Obara, Toru Imai, Hidenori Sato, Yuji Takeda, Takeo Kato, Kuniaki Ishii
Midnolin (MIDN) was first discovered in embryonic stem cells, but its physiological and pathological roles are, to date, poorly understood. In the present study, we therefore examined the role of MIDN in detail. We found that in PC12 cells, a model of neuronal cells, MIDN localized primarily to the nucleus and intracellular membranes. Nerve growth factor promoted MIDN gene expression, which was attenuated by specific inhibitors of extracellular signal-regulated kinases 1/2 and 5. MIDN-deficient PC12 cells created using CRISPR/Cas9 technology displayed significantly impaired neurite outgrowth...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724915/quinolinate-phosphoribosyltransferase-is-an-antiviral-host-factor-against-hepatitis-c-virus-infection
#7
Zhilong Wang, Yanhang Gao, Chao Zhang, Haiming Hu, Dongwei Guo, Yi Xu, Qiuping Xu, Weihong Zhang, Sisi Deng, Pingyun Lv, Yan Yang, Yanhua Ding, Qingquan Li, Changjiang Weng, Xinwen Chen, Sitang Gong, Hairong Chen, Junqi Niu, Hong Tang
HCV infection can decrease NAD(+)/NADH ratio, which could convert lipid metabolism to favor HCV replication. In hepatocytes, quinolinate phosphoribosyl transferase (QPRT) catabolizes quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN) for de novo NAD synthesis. However, whether and how HCV modulates QPRT hence the lipogenesis is unknown. In this work, we found QPRT was reduced significantly in livers of patients or humanized C/O(Tg) mice with persistent HCV infection. Mechanistic studies indicated that HCV NS3/4A promoted proteasomal degradation of QPRT through Smurf2, an E3 ubiquitin-protein ligase, in Huh7...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724888/crosscheck-an-open-source-web-tool-for-high-throughput-screen-data-analysis
#8
Jamil Najafov, Ayaz Najafov
Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724758/the-shcd-phosphotyrosine-adaptor-subverts-canonical-egf-receptor-trafficking
#9
Melanie K B Wills, Hayley R Lau, Nina Jones
Shc family signalling adaptors connect activated transmembrane receptors to proximal effectors, and most also contain a sequence involved in clathrin-mediated receptor endocytosis. Notably, this AP2 adaptin binding motif (AD) is absent from the ShcD homolog, which also uniquely promotes ligand-independent phosphorylation of the Epidermal Growth Factor (EGF) Receptor (EGFR). We now report that cultured cells expressing ShcD exhibit reduced EGF uptake, commensurate with a decrease in EGFR surface presentation...
July 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28724525/trim37-a-novel-e3-ligase-for-pex5-mediated-peroxisomal-matrix-protein-import
#10
Wei Wang, Zhi-Jie Xia, Jean-Claude Farré, Suresh Subramani
Most proteins destined for the peroxisomal matrix depend on the peroxisomal targeting signals (PTSs), which require the PTS receptor PEX5, whose deficiency causes fatal human peroxisomal biogenesis disorders (PBDs). TRIM37 gene mutations cause muscle-liver-brain-eye (mulibrey) nanism. We found that TRIM37 localizes in peroxisomal membranes and ubiquitylates PEX5 at K464 by interacting with its C-terminal 51 amino acids (CT51), which is required for PTS protein import. PEX5 mutations (K464A or ΔCT51), or TRIM37 depletion or mutation, reduce PEX5 abundance by promoting its proteasomal degradation, thereby impairing its functions in cargo binding and PTS protein import in human cells...
July 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28723672/e3-ubiquitin-ligase-tripartite-motif-containing-71-promotes-the-proliferation-of-non-small-cell-lung-cancer-through-the-inhibitor-of-kappab-%C3%AE-nuclear-factor-kappab-pathway
#11
Hongjiu Ren, Yitong Xu, Qiongzi Wang, Jun Jiang, Wudumuli, Linping Hui, Qingfu Zhang, Xiupeng Zhang, Enhua Wang, Limei Sun, Xueshan Qiu
Tripartite motif-containing (TRIM) 71 belongs to the TRIM protein family. Many studies have shown that TRIM71 plays conserved roles in stem cell proliferation, differentiation, and embryonic development; however, the relationship between TRIM71 and tumorigenesis is not clear. In this study, we demonstrate that TRIM71 expression in non-small cell lung cancer (NSCLC) is associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis. We found that TRIM71 was highly expressed in NSCLC cell lines compared with that in human normal bronchial epithelial cells...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722108/the-ubiquitin-ligase-scf-fbxw7%C3%AE-promotes-ata3-degradation
#12
Nan Song, Cheng Cao, Yiman Tang, Liyuan Bi, Yong Jiang, Yongsheng Zhou, Xin Song, Ling Liu, Wenshu Ge
GATA3 is a key transcription factor in cell fate determination and its dysregulation has been implicated in various types of malignancies. However, how the abundance and function of GATA3 are regulated remains unclear. Here, we report that GATA3 is physically associated with FBXW7α, and FBXW7α destabilizes GATA3 through assembly of a SKP1-CUL1-F-box E3 ligase complex. Importantly, we showed that FBXW7α promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7α inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7αis negatively correlated with that of GATA3 in breast cancer samples...
July 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#13
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen Andrew Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark John Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28720507/formation-and-degradation-of-nitrogen-mustard-induced-mgmt-dna-crosslinking-in-16hbe-cells
#14
Jin Cheng, Feng Ye, Guorong Dan, Yuanpeng Zhao, Jiqing Zhao, Zhongmin Zou
N-methyl-2,2-di(chloroethyl)amine (HN2) is a kind of bifunctional alkyltating agent, which can react with nucleophilic groups in DNA and/or protein to form HN2-bridged crosslinking of target molecules, such as DNA-protein crosslinkings (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme which solely repairs alkyl adduct on DNA directly. However, MGMT was detected to act as a protein cross-linked with DNA via alkylation in presence of HN2, and unexpectedly turned into a DNA damage enhancer in the form of MGMT-DNA cross-link (mDPC)...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28716524/the-e3-ligase-hectd3-promotes-esophageal-squamous-cell-carcinoma-escc-growth-and-cell-survival-through-targeting-and-inhibiting-caspase-9-activation
#15
Yi Li, Xiaowei Wu, Lin Li, Yongshuo Liu, Chengshan Xu, Dan Su, Zhihua Liu
Apoptosis resistance is an acquired hallmark of cancer cells and many factors can contribute to the tumor cell apoptosis resistance. In this study, we demonstrated that HECTD3, overexpressed in human esophageal squamous cell carcinoma (ESCC), confers cells resistance to cisplatin-induced apoptosis and promotes cancer cell survival. HECTD3 can bind and ubiquitinate caspase-9, which leads to inhibiting caspase-9 oligomerization and association with Apaf-1, and results in suppressing caspase-9 activation and inhibiting apoptosis...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28715909/ribosomal-stalling-during-translation-providing-substrates-for-ribosome-associated-protein-quality-control
#16
Claudio A P Joazeiro
Cells of all organisms survey problems during translation elongation, which may happen as a consequence of mRNA aberrations, inefficient decoding, or other sources. In eukaryotes, ribosome-associated quality control (RQC) senses elongation-stalled ribosomes and promotes dissociation of ribosomal subunits. This so-called ribosomal rescue releases the mRNA for degradation and allows 40S subunits to be recycled for new rounds of translation. However, the nascent polypeptide chains remain linked to tRNA and associated with the rescued 60S subunits...
July 17, 2017: Annual Review of Cell and Developmental Biology
https://www.readbyqxmd.com/read/28714848/hepatitis-b-virus-x-protein-activates-e3-ubiquitin-ligase-siah-1-to-control-virus-propagation-via-a-negative-feedback-loop
#17
Sujeong Yeom, Soo Shin Kim, Hyerin Jeong, Kyung Lib Jang
The seven in absentia homologue 1 (Siah-1) protein is an E3 ubiquitin ligase that induces ubiquitin-dependent proteasomal degradation of HBx, the principal regulatory protein of hepatitis B virus (HBV); however, its role in HBV propagation remains unknown. Here, we found that HBx upregulates Siah-1 levels in HepG2 but not in Hep3B cells, in which p53 is absent. For this effect, HBx sequentially activated ataxia telangiectasia mutated kinase and checkpoint kinase 2 via phosphorylation at the Ser-1981 and Thr-68 residues, respectively, which led to the activation of p53 via phosphorylation at the Ser-15 and Ser-20 residues...
July 17, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28714370/phosphatase-and-tensin-homolog-deleted-on-chromosome-10-degradation-induced-by-nedd4-promotes-acquired-erlotinib-resistance-in-non-small-cell-lung-cancer
#18
Huake Sun, Huiwen Ma, Jianmin Wang, Liqin Xia, Guangkuo Zhu, Zhoufei Wang, Jianguo Sun, Zhengtang Chen
Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors, such as gefitinib and erlotinib, is a critical issue in the treatment of patients with epidermal growth factor receptor mutant-positive non-small-cell lung cancer. Recent evidence suggests that downregulation of gene of phosphatase and tensin homolog deleted on chromosome 10 plays an important role in acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in various types of cancers, including lung cancer...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28714291/mechanism-of-midline-defect-causing-mutation-p151l-in-mid1-revealed
#19
Linda K Nicholson
The P151L mutation in the B-box1 domain of MID1 causes midline defects in X-linked Opitz G Syndrome. MID1 is known to be a key regulator of phosphatase PP2A through formation of a complex with its catalytic (PP2Ac) and regulatory (α4) subunits. Wright et al. show that this mutation retains B-box1 domain structure and E3 ligase activity (star) but blocks interaction with α4, indicating disruption of the MID1-α4-PP2Ac complex.
July 2017: FEBS Journal
https://www.readbyqxmd.com/read/28713400/overexpression-of-e3-ubiquitin-ligase-gene-adbil-contributes-to-resistance-against-chilling-stress-and-leaf-mold-disease-in-tomato
#20
Shuangchen Chen, Hongjiao Zhao, Mengmeng Wang, Jidi Li, Zhonghong Wang, Fenghua Wang, Airong Liu, Golam J Ahammed
Ubiquitination is a common regulatory mechanism, playing a critical role in diverse cellular and developmental processes in eukaryotes. However, a few reports on the functional correlation between E3 ubiquitin ligases and reactive oxygen species (ROS) or reactive nitrogen species (RNS) metabolism in response to stress are currently available in plants. In the present study, the E3 ubiquitin ligase gene AdBiL (Adi3 Binding E3 Ligase) was introduced into tomato line Ailsa Craig via Agrobacterium-mediated method...
2017: Frontiers in Plant Science
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