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https://www.readbyqxmd.com/read/28229932/csn5-jab1-suppresses-the-wnt-inhibitor-dkk1-in-colorectal-cancer-cells
#1
Sandra Jumpertz, Thomas Hennes, Yaw Asare, Anke K Schütz, Jürgen Bernhagen
The COP9 signalosome (CSN) is a multi-protein complex that is highly conserved in eukaryotes. Due to its regulatory impact on processes such as cell cycle, DNA damage response and apoptosis, the CSN is essential for mammalian cells. One of the best-studied functions of the CSN is the deNEDDylation of cullin-RING ligases (CRLs) via its catalytically active subunit CSN5/JAB1, thereby triggering the degradation of various target proteins. CSN5 was found to be overexpressed in many human cancer entities, including colon adenocarcinoma...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28225217/proteomic-analysis-of-the-cullin4b-interactome-using-proximity-dependent-biotinylation-in-living-cells
#2
Hailong Zhang, Shupeng Li, Pingting Liu, Frankie H F Lee, Albert H C Wong, Fang Liu
Cullin 4B (CUL4B) mutations have been implicated in mental retardation and dopamine-related behaviors due to disruptions in their interaction with Cullin-RING E3 ligases (CRLs). Thus, further identification of CUL4B substrates can increase the knowledge of protein homeostasis and illuminate the role of CUL4B in neuropsychiatric disease. However, the transient nature of the coupling between CUL4B and its substrates is difficult to detect in vivo using current approaches, thus hampers efforts to investigate functions of CRLs within unperturbed living systems...
February 22, 2017: Proteomics
https://www.readbyqxmd.com/read/28224653/air-sacculitis-in-three-rhesus-macaques-macaca-mulatta-and-one-japanese-macaque-m-%C3%A2-fuscata
#3
Cassandra O Cullin, Lois M A Colgin, Anne D Lewis
Bacterial infection of the laryngeal air sacs (air sacculitis) is infrequently reported in nonhuman primates, where it leads to chronic respiratory disease. It is particularly uncommon in macaques; however, we report here suppurative air sacculitis with extension to adjacent cervical tissues in three rhesus macaques and one Japanese macaque. Staphylococcus aureus, Streptococcus sp., and an anaerobic bacterium were isolated.
February 22, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28212551/nrip-dcaf6-stabilizes-the-androgen-receptor-protein-by-displacing-ddb2-from-the-cul4a-ddb1-e3-ligase-complex-in-prostate-cancer
#4
Hsin-Hsiung Chen, Ping Fan, Szu-Wei Chang, Yeou-Ping Tsao, Hsiang-Po Huang, Show-Li Chen
Both nuclear receptor interaction protein (NRIP) and DNA damage binding protein 2 (DDB2) belong to the Cullin 4 (CUL4)-DDB1 binding protein family and are androgen receptor (AR)-interacting proteins. Here, we investigated the expression patterns of the NRIP, DDB2 and AR proteins in human prostate cancer tissues and found that the expression levels of NRIP and AR were higher, but the DDB2 level was lower, in prostate cancer tissues than in non-neoplastic controls, suggesting NRIP as a candidate tumor promoter and DDB2 as a tumor suppressor in prostate cancer...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202763/inhibition-of-vpx-mediated-samhd1-and-vpr-mediated-hltf-degradation-by-selective-disruption-of-viral-crl4-dcaf1-e3-ubiquitin-ligase-assembly
#5
Hong Wang, Haoran Guo, Jiaming Su, Yajuan Rui, Wenwen Zheng, Wenying Gao, Wenyan Zhang, Zhaolong Li, Guanchen Liu, Wei Wei, Xiao-Fang Yu
The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or transcriptional factor HLTF, respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that post-translational modification (neddylation) of Cullin-4 is required for the activation of Vpx-CRL4 (DCAF1) E3 ligase. However, the mechanism of Vpx/Vpr-CRL4 (DCAF1) E3 ligase assembly is still poorly understood...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28181316/an-improved-method-for-purification-and-refolding-of-recombinant-hiv-vif-expressed-in-e-coli
#6
Carlos A Duarte, Mickel Palomino
Virion infectivity factor (Vif) is a 23 KDa protein which protects HIV-1 from deamination of its proviral DNA by APOBEC3G. The active form of Vif is a multimer that interacts simultaneously with CBF-beta, the Elongin B and C subunits, Cullin 5 and APOBEC3G to form a ubiquitin ligase complex targeting the latter for degradation. Vif clearly represents an attractive target for developing novel antiviral drugs for the therapy of HIV/AIDS, and this goal requires a source of well folded, readily available protein...
February 8, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28181263/alterations-of-intrinsic-tongue-muscle-properties-with-aging
#7
Miranda J Cullins, Nadine P Connor
INTRODUCTION: Age-related decline in the intrinsic lingual musculature could contribute to swallowing disorders, yet the effects of age on these muscles is unknown. We hypothesized reduced muscle fiber size and shifts to slower MyHC fiber types with age. METHODS: Intrinsic lingual muscles were sampled from 8 young-adult (9 months) and 8 old (32 months) Fischer 344/Brown Norway rats. Fiber size and MyHC were determined by fluorescent immunohistochemistry. RESULTS: Age was associated with a reduced abundance of rapidly-contracting muscle fibers, and more slowly-contracting fibers...
February 9, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28166272/activation-of-mapk-erk-signaling-by-burkholderia-pseudomallei-cycle-inhibiting-factor-cif
#8
Mei Ying Ng, Mei Wang, Patrick J Casey, Yunn-Hwen Gan, Thilo Hagen
Cycle inhibiting factors (Cifs) are virulence proteins secreted by the type III secretion system of some Gram-negative pathogenic bacteria including Burkholderia pseudomallei. Cif is known to function to deamidate Nedd8, leading to inhibition of Cullin E3 ubiquitin ligases (CRL) and consequently induction of cell cycle arrest. Here we show that Cif can function as a potent activator of MAPK/ERK signaling without significant activation of other signaling pathways downstream of receptor tyrosine kinases. Importantly, we found that the ability of Cif to activate ERK is dependent on its deamidase activity, but independent of Cullin E3 ligase inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28101194/inhibition-of-nedd8-and-fat10-ligase-activities-through-the-degrading-enzyme-nedd8-ultimate-buster-1-a-potential-anticancer-approach
#9
Ka-Liong Tan, Francesco Pezzella
The capabilities of tumour cells to survive through deregulated cell cycles and evade apoptosis are hallmarks of cancer. The ubiquitin-like proteins (UBL) proteasome system is important in regulating cell cycles via signaling proteins. Deregulation of the proteasomal system can lead to uncontrolled cell proliferation. The Skp, Cullin, F-box containing complex (SCF complex) is the predominant E3 ubiquitin ligase, and has diverse substrates. The ubiquitin ligase activity of the SCF complexes requires the conjugation of neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) to cullin proteins...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100625/the-ptpn14-tumour-suppressor-is-a-degradation-target-of-human-papillomavirus-e7
#10
Anita Szalmás, Vjekoslav Tomaić, Om Basukala, Paola Massimi, Suruchi Mittal, József Kónya, Lawrence Banks
: Activation of signalling pathways ensuring cell growth are essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumour suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signalling pathways. In this study we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28098200/cullin-7-mediates-proteasomal-and-lysosomal-degradations-of-rat-eag1-potassium-channels
#11
Po-Hao Hsu, Yu-Ting Ma, Ya-Ching Fang, Jing-Jia Huang, Yu-Ling Gan, Pei-Tzu Chang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Mammalian Eag1 (Kv10.1) potassium (K(+)) channels are widely expressed in the brain. Several mutations in the gene encoding human Eag1 K(+) channel have been associated with congenital neurodevelopmental anomalies. Currently very little is known about the molecules mediating protein synthesis and degradation of Eag1 channels. Herein we aim to ascertain the protein degradation mechanism of rat Eag1 (rEag1). We identified cullin 7 (Cul7), a member of the cullin-based E3 ubiquitin ligase family, as a novel rEag1 binding partner...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096463/deneddylase1-counters-automodification-of-neddylating-enzymes-to-maintain-nedd8-homeostasis-in-arabidopsis
#12
Julia Mergner, Bernhard Kuster, Claus Schwechheimer
In eukaryotes, the conjugation of the ubiquitin-like protein NEDD8 onto protein targets is an important post-translational modification. The best understood neddylation targets are the cullins, scaffold subunits of E3 ubiquitin ligases, where neddylation as well as deneddylation, facilitated by the protease activity of the CSN (COP9 signalosome), are required to control ubiquitin ligase assembly, function and ultimately substrate degradation. Little is known about the role of other deneddylating enzymes besides CSN and the role of neddylation and deneddylation of their substrates...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28089830/tumor-suppressor-spop-ubiquitinates-and-degrades-egln2-to-compromise-growth-of-prostate-cancer-cells
#13
Linli Zhang, Shan Peng, Xiangpeng Dai, Wenjian Gan, Xin Nie, Wenyi Wei, Guoqing Hu, Jianping Guo
EglN prolyl hydroxylases, a family of oxygen-sensing enzymes, hydroxylate distinct proteins to modulate diverse physiopathological signals. Aberrant regulations of EglNs result in multiple human diseases, including cancer. Different from EglN1 which function largely depends on the role of hypoxia-induce factor alpha (HIFα) in tumors, the functional significance and the upstream regulatory mechanisms of EglN2, especially in prostate cancer setting, remain largely unclear. Here, we demonstrated that dysregulation of EglN2 facilitated prostate cancer growth both in cells and in vivo...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#14
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28071842/tip-enhanced-raman-spectroscopy-to-distinguish-toxic-oligomers-from-a%C3%AE-1-42-fibrils-at-the-nanometer-scale
#15
Sébastien Bonhommeau, David Talaga, Julien Hunel, Christophe Cullin, Sophie Lecomte
For the first time, natural Aβ1-42 fibrils (WT) implicated in Alzheimer's disease, as well as two synthetic mutants forming less toxic amyloid fibrils (L34T) and highly toxic oligomers (oG37C), are chemically characterized at the scale of a single structure using tip-enhanced Raman spectroscopy (TERS). While the proportion of TERS features associated with amino acid residues is similar for the three peptides, a careful examination of amide I and amide III bands allows us to clearly distinguish WT and L34T fibers organized in parallel β-sheets from the small and more toxic oG37C oligomers organized in anti-parallel β-sheets...
January 10, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28052114/crl4wdr1-controls-polo-like-kinase-protein-abundance-to-promote-bilobe-duplication-basal-body-segregation-and-flagellum-attachment-in-trypanosoma-brucei
#16
Huiqing Hu, Qing Zhou, Xianxian Han, Ziyin Li
The Polo-like kinase homolog in Trypanosoma brucei, TbPLK, plays essential roles in basal body segregation, flagellum attachment and cytokinesis. The level of TbPLK protein is tightly controlled, but the underlying mechanism remains elusive. Here, we report a Cullin-RING ubiquitin ligase composed of Cullin4, the DNA damage-binding protein 1 homolog TbDDB1 and a WD40-repeat protein WDR1 that controls TbPLK abundance in the basal body and the bilobe. WDR1, through its C-terminal domain, interacts with the PEST motif in TbPLK and, through its N-terminal WD40 motif, binds to TbDDB1...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28035772/deregulated-neddylation-in-liver-fibrosis
#17
Imanol Zubiete-Franco, Pablo Fernández-Tussy, Lucía Barbier-Torres, Jorge Simon, David Fernández-Ramos, Fernando Lopitz-Otsoa, Virginia Gutiérrez-de Juan, Sergio López de Davalillo, Antonio Martín Duce, Paula Iruzubieta, Daniel Taibo, Javier Crespo, Juan Caballeria, Erica Villa, Igor Aurrekoetxea, Patricia Aspichueta, Marta Varela-Rey, Shelly C Lu, José M Mato, Naiara Beraza, Teresa C Delgado, María L Martínez-Chantar
: Hepatic fibrosis is a global health problem currently without effective therapeutic approaches. Even though the ubiquitin-like posttranslational modification of neddylation, that conjugates Nedd8 (neural precursor cell expressed developmentally downregulated) to specific targets, is aberrant in many pathologies, its relevance in liver fibrosis (LF) remained unexplored. Our results show deregulated neddylation in clinical fibrosis and both in mouse bileductligation- and CCl4 -induced fibrosis...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28032862/cullin-4-regulates-wingless-and-jnk-signaling-mediated-cell-death-in-the-drosophila-eye
#18
Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh
In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood...
December 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27987332/neddylated-cullin-3-is-required-for-vascular-endothelial-cadherin-mediated-endothelial-barrier-function
#19
Tomohisa Sakaue, Ayako Fujisaki, Hironao Nakayama, Masashi Maekawa, Hiromi Hiyoshi, Eiji Kubota, Takashi Joh, Hironori Izutani, Shigeki Higashiyama
Vascular endothelial-cadherin, a major endothelial adhesion molecule, regulates vascular permeability, and increased vascular permeability has been observed in several cancers. The aim of this study was to elucidate the role of the NEDD8-Cullin E3 ligase, in maintaining barrier permeability. To this end, we investigated the effects of the inhibition of Cullin E3 ligases, by using inhibitors and knockdown techniques in human umbilical vein endothelial cells. Further, we analyzed the mRNA and protein levels of the ligases by quantitative reverse transcription-polymerase chain reaction and western blotting, respectively...
December 17, 2016: Cancer Science
https://www.readbyqxmd.com/read/27983981/cul4a-functions-as-an-oncogene-in-ovarian-cancer-and-is-directly-regulated-by-mir-494
#20
Xiaoni Han, Ziling Fang, Heng Wang, Rongfang Jiao, Jing Zhou, Nian Fang
Cullin 4A (CUL4A), as a well-defined oncogene, has been reported to be upregulated in ovarian cancer clinically. However, the biological functions of CUL4A and the molecular mechanism underlying its upregulation in ovarian cancer remains unknown throughly. Here, we show that expression of CUL4A is significantly higher in ovarian cancer tissues compared to corresponding non-cancerous tissues. Moreover, silencing of CUL4A by siRNA markedly inhibits cell proliferation, invasion and epithelial-mesenchymal transition (EMT)...
October 27, 2016: Biochemical and Biophysical Research Communications
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