keyword
MENU ▼
Read by QxMD icon Read
search

cullin

keyword
https://www.readbyqxmd.com/read/28808481/cul4b-is-a-novel-prognostic-marker-in-cholangiocarcinoma
#1
Pengyu Li, Lili Zhang, Muyi Yang, Mei Qi, Xing Jin, Bo Han
Cullin 4B (Cul4B), a scaffold protein that assembles the ubiquitin ligase complex, is involved in a wide variety of physiological and developmental processes, such as cell cycle progression, DNA damage response and gene expression regulation. Cul4B is overexpressed in various solid tumors. However, the prognostic value and role of Cul4B in cholangiocarcinoma (CCA) is largely unknown. The present study demonstrated that Cul4B was overexpressed in 21 (26.6%) of 79 patients with intrahepatic CCA, and in 40 (28...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#2
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28805820/prostate-cancer-associated-spop-mutations-confer-resistance-to-bet-inhibitors-through-stabilization-of-brd4
#3
Xiangpeng Dai, Wenjian Gan, Xiaoning Li, Shangqian Wang, Wei Zhang, Ling Huang, Shengwu Liu, Qing Zhong, Jianping Guo, Jinfang Zhang, Ting Chen, Kouhei Shimizu, Francisco Beca, Mirjam Blattner, Divya Vasudevan, Dennis L Buckley, Jun Qi, Lorenz Buser, Pengda Liu, Hiroyuki Inuzuka, Andrew H Beck, Liewei Wang, Peter J Wild, Levi A Garraway, Mark A Rubin, Christopher E Barbieri, Kwok-Kin Wong, Senthil K Muthuswamy, Jiaoti Huang, Yu Chen, James E Bradner, Wenyi Wei
The bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins enhance the oncogenic functions of major cancer drivers by elevating the expression of these drivers, such as c-Myc in leukemia, or by promoting the transcriptional activities of oncogenic factors, such as AR and ERG in prostate cancer...
August 14, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28802844/structural-basis-for-cullins-and-ring-component-inhibition-targeting-e3-ubiquitin-pathway-conductors-for-cancer-therapeutics
#4
Shagufta Shafique, Waqar Ali, Sonia Kanwal, Sajid Rashid
Cullin (CUL)-RING E3 ubiquitin ligases (CRLs) are attractive therapeutic targets as they regulate diverse biological processes important for cancer cell survival by conferring substrate selectivity for ubiquitination and degradation. Given the complexity of CRL complexes, steps toward the structure-based design of small-molecule inhibitors to modulate their activity have remained elusive. In this study, we explored the structural assembly and interaction details of closely related CUL scaffolds (CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7) with RBX1 to screen potent small molecules against CRLs...
August 9, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28776949/structure-guided-design-of-peptides-as-tools-to-probe-the-protein-protein-interaction-between-cullin-2-and-elongin-bc-substrate-adaptor-in-cullin-ring-e3-ubiquitin-ligases
#5
Teresa Cardote, Alessio Ciulli
Cullin RING E3 ubiquitin ligases (CRLs) are large dynamic multi-subunit complexes that control the fate of many proteins in cells. CRLs constitute attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. Here we describe a structure-guided biophysical approach to probe the protein-protein interaction (PPI) between the Cullin-2 scaffold protein and the adaptor subunits Elongin BC within the context of the von Hippel-Lindau complex (CRL2VHL) using peptides...
August 3, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28717191/mln4924-pevonedistat-a-protein-neddylation-inhibitor-suppresses-proliferation-and-migration-of-human-clear-cell-renal-cell-carcinoma
#6
Shuai Tong, Yang Si, Hefen Yu, Lingqiang Zhang, Ping Xie, Wenguo Jiang
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715492/small-molecule-perturbation-of-the-cand1-cullin1-ubiquitin-cycle-stabilizes-p53-and-triggers-epstein-barr-virus-reactivation
#7
Nadezhda Tikhmyanova, Steve Tutton, Kayla A Martin, Fang Lu, Andrew V Kossenkov, Nicholas Paparoidamis, Shannon Kenney, Joseph M Salvino, Paul M Lieberman
The chemical probe C60 efficiently triggers Epstein-Barr Virus (EBV) reactivation from latency through an unknown mechanism. Here, we identify the Cullin exchange factor CAND1 as a biochemical target of C60. We also identified CAND1 in an shRNA library screen for EBV lytic reactivation. Gene expression profiling revealed that C60 activates the p53 pathway and protein analysis revealed a strong stabilization and S15 phosphorylation of p53. C60 reduced Cullin1 association with CAND1 and led to a global accumulation of ubiquitylated substrates...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28711427/temporal-remodeling-of-the-cell-cycle-accompanies-differentiation-in-the-drosophila-germline
#8
Taylor D Hinnant, Arturo A Alvarez, Elizabeth T Ables
Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28697798/a-proteomic-analysis-of-lrrk2-binding-partners-reveals-interactions-with-multiple-signaling-components-of-the-wnt-pcp-pathway
#9
Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients...
July 11, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28691927/ubiquitination-of-tumor-suppressor-pml-regulates-prometastatic-and-immunosuppressive-tumor-microenvironment
#10
Ya-Ting Wang, Jocelyn Chen, Chou-Wei Chang, Jayu Jen, Tzu-Yu Huang, Chun-Ming Chen, Roger Shen, Suh-Yuen Liang, I-Cheng Cheng, Shuenn-Chen Yang, Wu-Wei Lai, Kuang-Hung Cheng, Tao-Shih Hsieh, Ming-Zong Lai, Hung-Chi Cheng, Yi-Ching Wang, Ruey-Hwa Chen
The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells regulate the cell and non-cell constituents of surrounding stroma remains incompletely understood. Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in tumor microenvironment regulation is poorly characterized. PML is frequently downregulated in many cancer types, including lung cancer. Here, we identify a PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING ubiquitin ligase 4 (CRL4WDR4)...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28678234/a-tensegrity-driven-dna-nanopore
#11
O Mendoza, P Calmet, I Alves, S Lecomte, M Raoux, C Cullin, J Elezgaray
Control of transport across membranes, whether natural or synthetic, is fundamental in many biotechnology applications, including sensing and drug release. Mutations of naturally existing protein channels, such as hemolysin, have been explored in the past. More recently, DNA channels with conductivities in the nanosiemens range have been designed. Regulating transport across DNA channels in response to external stimuli remains an important challenge. Previous designs relied on steric hindrance to control the inner diameter of the channel, which resulted in unstable electric signatures...
July 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/28677427/cul4a-as-a-marker-and-potential-therapeutic-target-in-multiple-myeloma
#12
Yougang Yang, Shanan Wang, Jinghong Li, Shipeng Qi, Debing Zhang
Multiple myeloma is the most common cause of death of hematological malignancy worldwide. Cullin 4A has been proposed as oncogene in several types of human cancer, but the expression and function of cullin 4A in multiple myeloma remain unclear. Here, we demonstrate that cullin 4A plays an oncogenic role in multiple myeloma development. The expression of cullin 4A was detected by quantitative real-time polymerase chain reaction in multiple myeloma patients and multiple myeloma cell lines. In addition, silencing of cullin 4A with small interfering RNA was performed in human multiple myeloma cells, and the impact on proliferation, cell cycle, apoptosis, migration, and invasion of the multiple myeloma cells was analyzed...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28637452/downregulation-of-talin-1-expression-associates-with-increased-proliferation-and-migration-of-vascular-smooth-muscle-cells-in-aortic-dissection
#13
Xiaolong Wei, Yudong Sun, Yani Wu, Jiang Zhu, Bin Gao, Han Yan, Zhiqing Zhao, Jian Zhou, Zaiping Jing
BACKGROUND: This study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function. METHODS: Human aortic samples were obtained from organ donors who died from nonvascular diseases as normal controls and from patients undergoing surgical repair of thoracic aortic dissection. The expression level and distribution of Talin-1 were detected using westernblot analysis and immunohistochemistry in each sample...
June 20, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28630798/the-role-of-cullin4b-in-human-cancers
#14
REVIEW
Ying Li, Xin Wang
Cullin 4B (CUL4B) is a scaffold of the Cullin4B-Ring E3 ligase complex (CRL4B) that plays an important role in proteolysis and is implicated in tumorigenesis. Aberrant expression of CUL4B has been reported in various types of human diseases. Recently, studies have shown that CUL4B was overexpressed in a multitude of solid neoplasms and affect the expression of several tumor suppressor genes. In this review, we aim to summarize the biological function of CUL4B in order to better understand its pathogenesis in human cancers...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28623169/mutation-of-the-inhibitory-ethanol-site-in-gabaa-%C3%AF-1-receptors-promotes-tolerance-to-ethanol-induced-motor-incoordination
#15
Yuri A Blednov, Cecilia M Borghese, Carlos I Ruiz, Madeline A Cullins, Adriana Da Costa, Elizabeth A Osterndorff-Kahanek, Gregg E Homanics, R Adron Harris
Genes encoding the ρ1/2 subunits of GABAA receptors have been associated with alcohol (ethanol) dependence in humans, and ρ1 was also shown to regulate some of the behavioral effects of ethanol in animal models. Ethanol inhibits GABA-mediated responses in wild-type (WT) ρ1, but not ρ1(T6'Y) mutant receptors expressed in Xenopus laevis oocytes, indicating the presence of an inhibitory site for ethanol in the second transmembrane helix. In this study, we found that ρ1(T6'Y) receptors expressed in oocytes display overall normal responses to GABA, the endogenous GABA modulator (zinc), and partial agonists (β-alanine and taurine)...
September 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28620047/sccro-neddylates-cul3-to-selectively-promote-midbody-localization-and-activity-of-cul3klhl21-during-abscission
#16
Guochang Huang, Andrew J Kaufman, Ke Xu, Katia Manova, Bhuvanesh Singh
SCCRO/DCUN1D1, a component of the neddylation E3 complex, regulates the activity of the cullin-RING-ligase (CRL) type of ubiquitination E3s by promoting neddylation of cullin family members. Studies have shown SCCRO regulates proliferation in vitro and in vivo. Here, we show that inactivation of SCCRO results in prolonged mitotic time due to delayed and/or failed abscission. The effects of SCCRO on abscission involve its role in neddylation and localization of Cul3 to the midbody. The Cul3 adaptor KLHL21 mediates SCCRO's effects on abscission, as it fails to localize to the midbody in SCCRO-deficient cells during abscission and its inactivation resulted in phenotypic changes identical to SCCRO inactivation...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28619822/cop9-signalosome-subunits-protect-capicua-from-mapk-dependent-and-independent-mechanisms-of-degradation
#17
Annabelle Suisse, DanQing He, Kevin Legent, Jessica E Treisman
The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitylation by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28617828/erad-defects-and-the-hfe-h63d-variant-are-associated-with-increased-risk-of-liver-damages-in-alpha-1-antitrypsin-deficiency
#18
Philippe Joly, Hélène Vignaud, Julie Di Martino, Mathias Ruiz, Roman Garin, Lioara Restier, Abdelouahed Belmalih, Christelle Marchal, Christophe Cullin, Benoit Arveiler, Patricia Fergelot, Aaron D Gitler, Alain Lachaux, Julien Couthouis, Marion Bouchecareilh
BACKGROUND: The most common and severe disease causing allele of Alpha 1-Antitrypsin Deficiency (1ATD) is Z-1AT. This protein aggregates in the endoplasmic reticulum, which is the main cause of liver disease in childhood. Based on recent evidences and on the frequency of liver disease occurrence in Z-1AT patients, it seems that liver disease progression is linked to still unknown genetic factors. METHODS: We used an innovative approach combining yeast genetic screens with next generation exome sequencing to identify and functionally characterize the genes involved in 1ATD associated liver disease...
2017: PloS One
https://www.readbyqxmd.com/read/28604389/a-cullin-4b-ring-e3-ligase-complex-fine-tunes-pancreatic-%C3%AE-cell-paracrine-interactions
#19
Qing Li, Min Cui, Fan Yang, Na Li, Baichun Jiang, Zhen Yu, Daolai Zhang, Yijing Wang, Xibin Zhu, Huili Hu, Pei-Shan Li, Shang-Lei Ning, Si Wang, Haibo Qi, Hechen Song, Dongfang He, Amy Lin, Jingjing Zhang, Feng Liu, Jiajun Zhao, Ling Gao, Fan Yi, Tian Xue, Jin-Peng Sun, Yaoqin Gong, Xiao Yu
Somatostatin secreted by pancreatic δ cells mediates important paracrine interactions in Langerhans islets, including maintenance of glucose metabolism through the control of reciprocal insulin and glucagon secretion. Disruption of this circuit contributes to the development of diabetes. However, the precise mechanisms that control somatostatin secretion from islets remain elusive. Here, we found that a super-complex comprising the cullin 4B-RING E3 ligase (CRL4B) and polycomb repressive complex 2 (PRC2) epigenetically regulates somatostatin secretion in islets...
June 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28599312/cullin-3spop-ubiquitin-e3-ligase-promotes-the-poly-ubiquitination-and-degradation-of-hdac6
#20
Yuyong Tan, Yanpeng Ci, Xiangpeng Dai, Fei Wu, Jianping Guo, Deliang Liu, Brian J North, Jirong Huo, Jinfang Zhang
The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3SPOP earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines...
July 18, 2017: Oncotarget
keyword
keyword
59761
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"