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https://www.readbyqxmd.com/read/28428367/copii-coated-membranes-function-as-transport-carriers-of-intracellular-procollagen-i
#1
Amita Gorur, Lin Yuan, Samuel J Kenny, Satoshi Baba, Ke Xu, Randy Schekman
The coat protein complex II (COPII) is essential for the transport of large cargo, such as 300-nm procollagen I (PC1) molecules, from the endoplasmic reticulum (ER) to the Golgi. Previous work has shown that the CUL3-KLHL12 complex increases the size of COPII vesicles at ER exit sites to more than 300 nm in diameter and accelerates the secretion of PC1. However, the role of large COPII vesicles as PC1 transport carriers was not unambiguously demonstrated. In this study, using stochastic optical reconstruction microscopy, correlated light electron microscopy, and live-cell imaging, we demonstrate the existence of mobile COPII-coated vesicles that completely encapsulate the cargo PC1 and are physically separated from ER...
April 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28414128/impaired-degradation-of-medullary-wnk4-in-the-kidneys-of-klhl2-knockout-mice
#2
Yuri Kasagi, Daiei Takahashi, Tomomi Aida, Hidenori Nishida, Naohiro Nomura, Moko Zeniya, Takayasu Mori, Emi Sasaki, Fumiaki Ando, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), and Cullin3 (CUL3) genes were identified as being responsible for hereditary hypertensive disease pseudohypoaldosteronism type II (PHAII). Normally, the KLHL3/CUL3 ubiquitin ligase complex degrades WNKs. In PHAII, the loss of interaction between KLHL3 and WNK4 increases levels of WNKs because of impaired ubiquitination, leading to abnormal over-activation of the WNK-OSR1/SPAK-NCC cascade in the kidney's distal convoluted tubules (DCT)...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28395323/defining-the-human-sperm-microtubulome-an-integrated-genomics-approach%C3%A2
#3
Fanny Jumeau, Frédéric Chalmel, Francisco-Jose Fernandez-Gomez, Céline Carpentier, Hélène Obriot, Meryem Tardivel, Marie-Laure Caillet-Boudin, Jean-Marc Rigot, Nathalie Rives, Luc Buée, Nicolas Sergeant, Valérie Mitchell
Sperm motility notably depends on the structural integrity of the flagellum and the regulation of microtubule dynamics. Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders)...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28280036/myeloid-derived-cullin-3-promotes-stat3-phosphorylation-by-inhibiting-ogt-expression-and-protects-against-intestinal-inflammation
#4
Xinghui Li, Zhibin Zhang, Lupeng Li, Wei Gong, Audrey J Lazenby, Benjamin J Swanson, Laura E Herring, John M Asara, Jeffrey D Singer, Haitao Wen
Signal transducer and activator of transcription 3 (STAT3) is a key mediator of intestinal inflammation and tumorigenesis. However, the molecular mechanism that modulates STAT3 phosphorylation and activation is not fully understood. Here, we demonstrate that modification of STAT3 with O-linked β-N-acetylglucosamine (O-GlcNAc) on threonine 717 (T717) negatively regulates its phosphorylation and targets gene expression in macrophages. We further found that cullin 3 (CUL3), a cullin family E3 ubiquitin ligase, down-regulates the expression of the O-GlcNAc transferase (OGT) and inhibits STAT3 O-GlcNAcylation...
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28222034/three-cases-of-gordon-syndrome-with-dominant-klhl3-mutations
#5
Ji Soo Park, Eujin Park, Hye Sun Hyun, Yo Han Ahn, Hee Gyung Kang, Il-Soo Ha, Hae Il Cheong
BACKGROUND: Gordon syndrome (GS) is a rare form of monogenic hypertension characterized by low renin hypertension, hyperkalemia, hyperchloremic metabolic acidosis, and normal glomerular filtration rate. To date, four genes causing GS have been identified as: WNK1, WNK4, CUL3, and KLHL3. CASE PRESENTATION: We report three cases of GS in two families. All patients presented with typical clinical features of GS and had a known dominant KLHL3 mutation. Oral thiazide treatment with low salt diet resulted in normalization of blood pressure and serum electrolytes in all three cases...
March 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/28220917/ditopic-receptors-containing-urea-groups-for-solvent-extraction-of-cu-ii-salts
#6
Israel Carreira-Barral, Marta Mato-Iglesias, Andrés de Blas, Carlos Platas-Iglesias, Peter A Tasker, David Esteban-Gómez
The ditopic receptor L3 [1-(2-((7-(4-(tert-butyl)benzyl)-1,4,7,10-tetraazacyclododecan-1-yl)methyl)phenyl)-3-(3-nitrophenyl)urea] containing a macrocyclic cyclen unit for Cu(ii)-coordination and a urea moiety for anion binding was designed for recognition of metal salts. The X-ray structure of [CuL3(SO4)] shows that the sulfate anion is involved in cooperative binding via coordination to the metal ion and hydrogen-bonding to the urea unit. This behaviour is similar to that observed for the related receptor L1 [1-(2-((bis(pyridin-2-ylmethyl)amino)methyl)phenyl)-3-(3-nitrophenyl)urea], which forms a dimeric [CuL1(μ-SO4)]2 structure in the solid state...
February 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28216678/the-cul3-spop-daxx-axis-is-a-novel-regulator-of-vegfr2-expression-in-vascular-endothelial-cells
#7
Tomohisa Sakaue, Iori Sakakibara, Takahiro Uesugi, Ayako Fujisaki, Koh-Ichi Nakashiro, Hiroyuki Hamakawa, Eiji Kubota, Takashi Joh, Yu-Ki Imai, Hironori Izutani, Shigeki Higashiyama
Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202604/retraction-antioxidant-induced-inrf2-keap1-tyrosine-85-phosphorylation-controls-the-nuclear-export-and-degradation-of-the-inrf2-cul3-rbx1-complex-to-allow-normal-nrf2-activation-and-repression
#8
James W Kaspar, Suryakant K Niture, Anil K Jaiswal
No abstract text is available yet for this article.
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28178566/wnk-kinase-signaling-in-ion-homeostasis-and-human-disease
#9
REVIEW
Masoud Shekarabi, Jinwei Zhang, Arjun R Khanna, David H Ellison, Eric Delpire, Kristopher T Kahle
WNK kinases, along with their upstream regulators (CUL3/KLHL3) and downstream targets (the SPAK/OSR1 kinases and the cation-Cl(-) cotransporters [CCCs]), comprise a signaling cascade essential for ion homeostasis in the kidney and nervous system. Recent work has furthered our understanding of the WNKs in epithelial transport, cell volume homeostasis, and GABA signaling, and uncovered novel roles for this pathway in immune cell function and cell proliferation.
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28159762/prothymosin-%C3%AE-mediates-nuclear-import-of-the-inrf2-cul3%C3%A2-rbx1-complex-to-degrade-nuclear-nrf2
#10
Suryakant K Niture, Anil K Jaiswal
No abstract text is available yet for this article.
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28115426/p97-negatively-regulates-nrf2-by-extracting-ubiquitylated-nrf2-from-the-keap1-cul3-e3-complex
#11
Shasha Tao, Pengfei Liu, Gang Luo, Montserrat Rojo de la Vega, Heping Chen, Tongde Wu, Joseph Tillotson, Eli Chapman, Donna D Zhang
Activation of the stress-responsive transcription factor NRF2 is the major line of defense to combat oxidative or electrophilic insults. Under basal conditions, NRF2 is continuously ubiquitylated by the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex and is targeted to the proteasome for degradation (the canonical mechanism). However, the path from the CUL3 complex to ultimate proteasomal degradation was previously unknown. p97 is a ubiquitin-targeted ATP-dependent segregase that extracts ubiquitylated client proteins from membranes, protein complexes, or chromatin and has an essential role in autophagy and the ubiquitin proteasome system (UPS)...
April 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28100706/oscul3a-negatively-regulates-cell-death-and-immunity-by-degrading-osnpr1-in-rice
#12
Qunen Liu, Yuese Ning, Yingxin Zhang, Ning Yu, Chunde Zhao, Xiaodeng Zhan, Weixun Wu, Daibo Chen, Xiangjin Wei, Guo-Liang Wang, Shihua Cheng, Liyong Cao
Cullin3-based RING E3 ubiquitin ligases (CRL3), composed of Cullin3 (CUL3), RBX1, and BTB proteins, are involved in plant immunity, but the function of CUL3 in the process is largely unknown. Here, we show that rice (Oryza sativa) OsCUL3a is important for the regulation of cell death and immunity. The rice lesion mimic mutant oscul3a displays a significant increase in the accumulation of flg22- and chitin-induced reactive oxygen species, and in pathogenesis-related gene expression as well as resistance to Magnaporthe oryzae and Xanthomonas oryzae pv oryzae...
February 2017: Plant Cell
https://www.readbyqxmd.com/read/28052936/klhl3-knockout-mice-reveal-the-physiological-role-of-klhl3-and-the-pathophysiology-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#13
Emi Sasaki, Koichiro Susa, Takayasu Mori, Kiyoshi Isobe, Yuya Araki, Yuichi Inoue, Yuki Yoshizaki, Fumiaki Ando, Yutaro Mori, Shintaro Mandai, Moko Zeniya, Daiei Takahashi, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII). It was recently demonstrated that this results from the defective degradation of WNK1 and WNK4 by the KLHL3/CUL3 ubiquitin ligase complex. However, the other physiological in vivo roles of KLHL3 remain unclear. Therefore, here we generated KLHL3(-/-) mice that expressed β-galactosidase (β-Gal) under the control of the endogenous KLHL3 promoter...
April 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28035139/mitochondrial-pkm2-regulates-oxidative-stress-induced-apoptosis-by-stabilizing-bcl2
#14
Ji Liang, Ruixiu Cao, Xiongjun Wang, Yajuan Zhang, Pan Wang, Hong Gao, Chen Li, Fan Yang, Rong Zeng, Ping Wei, Dawei Li, Wenfeng Li, Weiwei Yang
Pyruvate kinase M2 isoform (PKM2) catalyzes the last step of glycolysis and plays an important role in tumor cell proliferation. Recent studies have reported that PKM2 also regulates apoptosis. However, the mechanisms underlying such a role of PKM2 remain elusive. Here we show that PKM2 translocates to mitochondria under oxidative stress. In the mitochondria, PKM2 interacts with and phosphorylates Bcl2 at threonine (T) 69. This phosphorylation prevents the binding of Cul3-based E3 ligase to Bcl2 and subsequent degradation of Bcl2...
March 2017: Cell Research
https://www.readbyqxmd.com/read/28011395/salvianolic-acid-a-ameliorates-the-integrity-of-blood-spinal-cord-barrier-via-mir-101-cul3-nrf2-ho-1-signaling-pathway
#15
De-Shui Yu, Yan-Song Wang, Yun-Long Bi, Zhan-Peng Guo, Ya-Jiang Yuan, Song-Ming Tong, Rui-Chao Su, Li-Hao Ge, Jian Wang, Ya-Li Pan, Ting-Ting Guan, Yang Cao
Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10 mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24 h post-SCI...
December 20, 2016: Brain Research
https://www.readbyqxmd.com/read/27941885/dbc2-rhobtb2-functions-as-a-tumor-suppressor-protein-via-musashi-2-ubiquitination-in-breast-cancer
#16
Y M Choi, K B Kim, J H Lee, Y K Chun, I S An, S An, S Bae
The gene encoding 'deleted in breast cancer 2' (DBC2), also referred to as RHOBTB2 (Rho-related BTB domain-containing protein 2), is classified as a tumor suppressor gene. DBC2 is a substrate-specific adaptor protein for a novel class of Cullin-3 (CUL3)-based E3 ubiquitin ligases; however, it is unclear if the substrate adaptor function of DBC2 is required for its tumor suppressor activity. Furthermore, the key substrates of DBC2-mediated ubiquitination have yet to be identified. In the present study, we established a genome-wide human cDNA library-based in vitro ubiquitination target screening assay and identified Musashi-2 (MSI2) as a novel ubiquitination target protein of DBC2...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27930311/spop-promotes-skeletal-development-and-homeostasis-by-positively-regulating-ihh-signaling
#17
Hongchen Cai, Aimin Liu
Indian Hedgehog (Ihh) regulates chondrocyte and osteoblast differentiation through the Glioma-associated oncogene homolog (Gli) transcription factors. Previous in vitro studies suggested that Speckle-type POZ protein (Spop), part of the Cullin-3 (Cul3) ubiquitin ligase complex, targets Gli2 and Gli3 for degradation and negatively regulates Hedgehog (Hh) signaling. In this study, we found defects in chondrocyte and osteoblast differentiation in Spop-null mutant mice. Strikingly, both the full-length and repressor forms of Gli3, but not Gli2, were up-regulated in Spop mutants, and Ihh target genes Patched 1 (Ptch1) and parathyroid hormone-like peptide (Pthlh) were down-regulated, indicating compromised Hh signaling...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27890723/global-gene-expression-changes-in-the-prefrontal-cortex-of-rabbits-with-hypercholesterolemia-and-or-hypertension
#18
Sau-Yeen Loke, Peter Tsun-Hon Wong, Wei-Yi Ong
Although many studies have identified a link between hypercholesterolemia or hypertension and cognitive deficits, till date, comprehensive gene expression analyses of the brain under these conditions is still lacking. The present study was carried out to elucidate differential gene expression changes in the prefrontal cortex (PFC) of New Zealand white rabbits exposed to hypercholesterolemia and/or hypertension with a view of identifying gene networks at risk. Microarray analyses of the PFC of hypercholesterolemic rabbits showed 850 differentially expressed genes (DEGs) in the cortex of hypercholesterolemic rabbits compared to controls, but only 5 DEGs in hypertensive rabbits compared to controls...
November 25, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27882355/cullin-3-mutation-causes-arterial-stiffness-and-hypertension-through-a-vascular-smooth-muscle-mechanism
#19
Larry N Agbor, Stella-Rita C Ibeawuchi, Chunyan Hu, Jing Wu, Deborah R Davis, Henry L Keen, Frederick W Quelle, Curt D Sigmund
Cullin-3 (CUL3) mutations (CUL3Δ9) were previously identified in hypertensive patients with pseudohypoaldosteronism type-II (PHAII), but the mechanism causing hypertension and whether this is driven by renal tubular or extratubular mechanisms remains unknown. We report that selective expression of CUL3Δ9 in smooth muscle acts by interfering with expression and function of endogenous CUL3, resulting in impaired turnover of the CUL3 substrate RhoA, increased RhoA activity, and augmented RhoA/Rho kinase signaling...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27827994/ibtk-differently-modulates-gene-expression-and-rna-splicing-in-hela-and-k562-cells
#20
Giuseppe Fiume, Annarita Scialdone, Francesca Rizzo, Maria Rosaria De Filippo, Carmelo Laudanna, Francesco Albano, Gaetanina Golino, Eleonora Vecchio, Marilena Pontoriero, Selena Mimmi, Simona Ceglia, Antonio Pisano, Enrico Iaccino, Camillo Palmieri, Sergio Paduano, Giuseppe Viglietto, Alessandro Weisz, Giuseppe Scala, Ileana Quinto
The IBTK gene encodes the major protein isoform IBTKα that was recently characterized as substrate receptor of Cul3-dependent E3 ligase, regulating ubiquitination coupled to proteasomal degradation of Pdcd4, an inhibitor of translation. Due to the presence of Ankyrin-BTB-RCC1 domains that mediate several protein-protein interactions, IBTKα could exert expanded regulatory roles, including interaction with transcription regulators. To verify the effects of IBTKα on gene expression, we analyzed HeLa and K562 cell transcriptomes by RNA-Sequencing before and after IBTK knock-down by shRNA transduction...
November 7, 2016: International Journal of Molecular Sciences
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