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Yuyong Tan, Deliang Liu, Jian Gong, Jia Liu, Jirong Huo
F-box only protein 31 (FBXO31), initially identified in 2005, is a novel subunit of the S-phase kinase associated protein 1-Cullin 1-F-box ubiquitin ligase. As with other F-box proteins, FBXO31 may interact with several proteins to promote their ubquitination and subsequent degradation in an F-box-dependent manner. It has been revealed that FBXO31 serves a crucial role in DNA damage response and tumorigenesis. However, the expression and function of FBXO31 varies in different types of human cancer. To the best of our knowledge, the present review is the first to summarize the role of FBXO31 in different types of human cancer and determine its underlying mechanisms, thereby paving the road for the design of FBXO31-targeted anticancer therapies...
April 2018: Oncology Letters
Christos Spanos, Elaina M Maldonado, Ciarán P Fisher, Petchpailin Leenutaphong, Ernesto Oviedo-Orta, David Windridge, Francisco J Salguero, Alexandra Bermúdez-Fajardo, Mark E Weeks, Caroline Evans, Bernard M Corfe, Naila Rabbani, Paul J Thornalley, Michael H Miller, Huan Wang, John F Dillon, Alberto Quaglia, Anil Dhawan, Emer Fitzpatrick, J Bernadette Moore
Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE-/- ) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS)...
2018: Proteome Science
Xi Yang, Felichi Mae Arines, Weichao Zhang, Ming Li
The yeast Dsc E3 ligase complex has long been recognized as a Golgi-specific protein ubquitination system. It shares a striking sequence similarity to the Hrd1 complex that plays critical roles in the ER-associated degradation pathway. Using biochemical purification and mass spectrometry, we identified two novel Dsc subunits, which we named as Gld1 and Vld1. Surprisingly, Gld1 and Vld1 do not coexist in the same complex. Instead, they compete with each other to form two functionally independent Dsc subcomplexes...
January 22, 2018: ELife
Qin M Chen, Anthony J Maltagliati
The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating the expression of antioxidant and detoxification genes. Gene knockout approaches have demonstrated its universal cytoprotective features. While Nrf2 has been the topic of intensive research in cancer biology since its discovery in 1994, understanding the role of Nrf2 in cardiovascular disease has just begun. The literature concerning Nrf2 in experimental models of atherosclerosis, ischemia, reperfusion, cardiac hypertrophy, heart failure, and diabetes supports its cardiac protective character...
February 1, 2018: Physiological Genomics
Hongbiao Huang, Ni Liu, Yuning Liao, Ningning Liu, Jianyu Cai, Xiaohong Xia, Zhiqiang Guo, Yanling Li, Qirong Wen, Qi Yin, Yan Liu, Qingxia Wu, Dhivya Rajakumar, Xiujie Sheng, Jinbao Liu
BACKGROUND: Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent. METHOD: MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis...
June 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
Anna R Busija, Hemal H Patel, Paul A Insel
Caveolins (Cavs) are ~20 kDa scaffolding proteins that assemble as oligomeric complexes in lipid raft domains to form caveolae, flask-shaped plasma membrane (PM) invaginations. Caveolae ("little caves") require lipid-lipid, protein-lipid, and protein-protein interactions that can modulate the localization, conformational stability, ligand affinity, effector specificity, and other functions of proteins that are partners of Cavs. Cavs are assembled into small oligomers in the endoplasmic reticulum (ER), transported to the Golgi for assembly with cholesterol and other oligomers, and then exported to the PM as an intact coat complex...
April 1, 2017: American Journal of Physiology. Cell Physiology
Lihua Sun, Chao Xu, Guoqing Chen, Min Yu, Songwei Yang, Yuan Qiu, Ke Peng, Wensheng Wang, Weidong Xiao, Hua Yang
OS-9 is a lectin required for efficient ubquitination of glycosylated substrates of endoplasmic reticulum-associated degradation (ERAD). OS-9 has previously been implicated in ER-to-Golgi transport and transcription factor turnover. However, we know very little about other functions of OS-9 under endoplasmic reticulum stress. Here, we used gene knockdown and overexpression approaches to study the protective effect of OS-9 on intestinal barrier function of intestinal epithelial cell Caco-2 monolayer. We found that OS-9 attenuated intestinal epithelial barrier dysfunction under hypoxia through up-regulating occludin and claudin-1 protein expression...
2015: International Journal of Biological Sciences
Renliang Yang, Chuan-Fa Liu
In eukaryotic cells, many proteins undergo extensive post-translational modifications (PTMs) such as methylation, acetylation, phosphorylation, glycosylation, and ubiquitination. Among these, ubiquitination is a particularly interesting PTM from both structural and functional viewpoints. In ubiquitination, the C-terminal carboxyl group of the small ubiquitin protein is attached to the ε-amine of a lysine residue of a substrate protein through an isopeptide bond. Ubiquitination has been shown to be involved in the regulation of many cellular processes including protein degradation and gene expression...
2015: Topics in Current Chemistry
Albert Escobedo, Tiago Gomes, Eric Aragón, Pau Martín-Malpartida, Lidia Ruiz, Maria J Macias
We investigated the mechanisms of activation and degradation of the E3 ubiquitin ligase Nedd4L combining the available biochemical information with complementary biophysical techniques. Using nuclear magnetic resonance spectroscopy, we identified that the C2 domain binds Ca(2+) and inositol 1,4,5-trisphosphate (IP3) using the same interface that is used to interact with the HECT domain. Thus, we propose that the transition from the closed to the active form is regulated by a competition of IP3 and Ca(2+) with the HECT domain for binding to the C2 domain...
October 7, 2014: Structure
Rosa Rubino, Valentino Bezzerri, Maria Favia, Marcella Facchini, Maela Tebon, Anurag Kumar Singh, Brigitte Riederer, Ursula Seidler, Antonio Iannucci, Alessandra Bragonzi, Giulio Cabrini, Stephan J Reshkin, Anna Tamanini
Pseudomonas aeruginosa infections of the airway cells decrease apical expression of both wild-type (wt) and F508del CFTR through the inhibition of apical endocytic recycling. CFTR endocytic recycling is known to be regulated by its interaction with PDZ domain containing proteins. Recent work has shown that the PDZ domain scaffolding protein NHERF1 finely regulates both wt and F508delCFTR membrane recycling. Here, we investigated the effect of P. aeruginosa infection on NHERF1 post-translational modifications and how this affects CFTR expression in bronchial epithelial cells and in murine lung...
December 2014: Pflügers Archiv: European Journal of Physiology
Yan Meng, Chen Chen, Lei Wang, Xia Wang, Cui Tian, Jie Du, Hui-Hua Li
BACKGROUND: Peptidoglycan (PGN) is a component of cell wall in Gram-positive bacteria that stimulates inflammatory responses through Toll-like receptor 2 (TLR2). The carboxyl terminus of constitutive heat shock cognate 70 (HSC70)-interacting protein (CHIP, also known as Stub1) is a U-box-type E3 ubiquitin ligase, which plays an important role in protein quality control and inflammation through ubquitin-mediated proteasomal degradation. However, it is unclear whether TLR2 agonist PGN regulates the expression and activation of CHIP...
2013: Cellular Physiology and Biochemistry
(no author information available yet)
No abstract text is available yet for this article.
August 22, 2013: Molecular Cell
Xiaoli Tang, Sicheng Wen, Dong Zheng, Lynne Tucker, Lulu Cao, Dennis Pantazatos, Steven F Moss, Bharat Ramratnam
The RNase III enzyme Drosha initiates microRNA (miRNA) biogenesis in the nucleus by cleaving primary miRNA transcripts into shorter precursor molecules that are subsequently exported into the cytoplasm for further processing. While numerous disease states appear to be associated with aberrant expression of Drosha, the molecular mechanisms that regulate its protein levels are largely unknown. Here, we report that ubiquitination and acetylation regulate Drosha protein levels oppositely. Deacetylase inhibitors trichostatin A (TSA) and nicotinamide (NIA) increase Drosha protein level as measured by western blot but have no effects on its mRNA level in HEK293T cells...
2013: PloS One
Sang-Wang Lee, Hyesook Youn, Eun-Joo Kim, Soo-Jong Um
Despite the importance of retinoic acid (RA) signaling and histone monoubiquitination in determining cell fate, the underlying mechanism linking the two processes is poorly explored. We describe that additional sex comb-like 1 (ASXL1) represses RA receptor activity by cooperating with BRCA1-associated protein 1 (BAP1), which contains the ubiquitin C-terminal hydrolase (UCH) domain. Both the UCH- and ASXL1-binding domains of BAP1 were required for cooperation. In contrast to Drosophila BAP1, mammalian BAP1 cleaved ubiquitin from histone H2B...
July 25, 2013: Molecular Cell
Manoj M Lalu, Han Xu, Sowndramalingam Sankaralingam, Sandra T Davidge
BACKGROUND: The proteasome degrades ubiquitinated proteins and is the major pathway for intracellular protein degradation. The role of the proteasome in endothelial dysfunction observed in septic shock remains unknown. We stimulated primary cultures of human umbilical vein endothelial cells with lipopolysaccharide (LPS) and investigated effects on the proteasome. We hypothesized that proteasome inhibition would decrease endothelial cell activation, oxidative stress, and alter the proteome...
October 2012: Journal of Cardiovascular Pharmacology
Zhi-dong Zhou, Christine Hui-shan Chan, Zhi-cheng Xiao, Eng-king Tan
Recent findings suggest that Ring finger protein 146 (RNF146), also called iduna, have neuroprotective property due to its inhibition of Parthanatos via binding with Poly(ADP-ribose) (PAR). The Parthanatos is a PAR dependent cell death that has been implicated in many human diseases. RNF146/Iduna acts as a PARsylation-directed E3 ubquitin ligase to mediate tankyrase-dependent degradation of axin, thereby positively regulates Wnt signaling. RNF146/Iduna can also facilitate DNA repair and protect against cell death induced by DNA damaging agents or γ-irradiation...
November 2011: Cell Adhesion & Migration
Jinsuk Kang, Ben Goodman, Yixian Zheng, Dean Tantin
BACKGROUND: Transcription factor Oct1 regulates multiple cellular processes. It is known to be phosphorylated during the cell cycle and by stress, however the upstream kinases and downstream consequences are not well understood. One of these modified forms, phosphorylated at S335, lacks the ability to bind DNA. Other modification states besides phosphorylation have not been described. METHODOLOGY/PRINCIPAL FINDINGS: We show that Oct1 is phosphorylated at S335 in the Oct1 DNA binding domain during M-phase by the NIMA-related kinase Nek6...
2011: PloS One
Shu H Chen, Ankur H Shah, Nava Segev
Ypt/Rab GTPases are conserved molecular switches that regulate the different steps of intracellular trafficking pathways. In yeast, the Ypt31/32 GTPases are required for exit from the trans-Golgi and for recycling from the plasma membrane (PM), through early endosomes, to the Golgi. We have previously shown that the recycling function of Ypt31/32 is mediated by an effector called Rcy1. Specifically, both Ypt31/32 and Rcy1 are required for recycling the vSNARE Snc1. Rcy1 contains an F-box domain shared by proteins that act in substrate recognition of ubiquitin ligases...
January 2011: Cellular Logistics
Aoife Gowran, Carrie E Murphy, Veronica A Campbell
The phytocannabinoid Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the main psychoactive cannabinoid in cannabis, activates a number of signalling cascades including p53. This study examines the role of Delta(9)-THC in regulating the p53 post-translational modifier proteins, Murine double minute (Mdm2) and Small Ubquitin-like MOdifier protein 1 (SUMO-1) in cortical neurons. Delta(9)-THC increased both Mdm2 and SUMO-1 protein expression and induced the deSUMOylation of p53 in a cannabinoid receptor type 1 (CB(1))-receptor dependent manner...
November 3, 2009: FEBS Letters
Felicity Alcock, Eileithyia Swanton
Proteins that fail to fold or assemble with partner subunits are selectively removed from the endoplasmic reticulum (ER) via the ER-associated degradation (ERAD) pathway. Proteins selected for ERAD are polyubiquitinated and retrotranslocated into the cytosol for degradation by the proteasome. Although it is unclear how proteins are initially identified by the ERAD system in mammalian cells, OS-9 was recently proposed to play a key role in this process. Here we show that OS-9 is upregulated in response to ER stress and is associated both with components of the ERAD machinery and with ERAD substrates...
January 30, 2009: Journal of Molecular Biology
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