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Adaptor protein 2

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https://www.readbyqxmd.com/read/28818995/maternal-dcaf2-is-crucial-for-maintenance-of-genome-stability-during-the-first-cell-cycle-in-mice
#1
Yi-Wen Xu, Lan-Rui Cao, Min Wang, Ying Xu, Xin Wu, Junping Liu, Chao Tong, Heng-Yu Fan
Precise regulation of DNA replication and genome integrity is crucial for gametogenesis and early embryogenesis. Cullin ring-finger ubiquitin ligase 4 (CRL4) has multiple functions in the maintenance of germ cell survival, oocyte meiotic maturation, and maternal-zygotic transition in mammals. DDB1-cullin 4-associated factor-2 (DCAF2, also known as DTL or CDT2) is an evolutionarily conserved substrate receptor of CRL4. To determine whether DCAF2 is a key CRL4 substrate adaptor in mammalian oocytes, we generated a novel mouse strain that carries a Dcaf2 allele flanked by LoxP sequences, and specifically deleted Dcaf2 in oocytes...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28808088/the-armadillo-protein-p0071-controls-kif3-motor-transport
#2
Alexander Becher, Tim Eiseler, Marc Porzner, Paul Walther, René Keil, Susanne Bobrovich, Mechthild Hatzfeld, Thomas Seufferlein
We here report a novel function of the armadillo protein p0071 during KIF3/kinesin-2-mediated transport. Secretion of chromogranin A and matrix metallopeptidase 9 from pancreatic neuroendocrine tumor cells or pancreatic cancer cells, respectively, was substantially reduced following knockdown of p0071. Vesicle tracking indicated impaired directional persistence of vesicles upon p0071 depletion. This suggests a disturbed balance between plus- and minus-end directed microtubule transport in cells lacking p0071...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28807996/klhl6-deficiency-impairs-transitional-b-cell-survival-and-differentiation
#3
Barbara Bertocci, Damiana Lecoeuche, Delphine Sterlin, Julius Kühn, Baptiste Gaillard, Annie De Smet, Frederique Lembo, Christine Bole-Feysot, Nicolas Cagnard, Tatiana Fadeev, Auriel Dahan, Jean-Claude Weill, Claude-Agnès Reynaud
Klhl6 belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. Several of these proteins function as adaptors of the Cullin3 E3 ubiquitin ligase complex. In this article, we report that Klhl6 deficiency induces, as previously described, a 2-fold reduction in mature B cells. However, we find that this deficit is centered on the inability of transitional type 1 B cells to survive and to progress toward the transitional type 2 B cell stage, whereas cells that have passed this step generate normal germinal centers (GCs) upon a T-dependent immune challenge...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28791343/breast-cancer-associated-gene-3-interacts-with-rac1-and-augments-nf-%C3%AE%C2%BAb-signaling-in-vitro-but-has-no-effect-on-rankl-induced-bone-resorption-in-vivo
#4
Chen Yao, Kuan-Ping Yu, William Philbrick, Ben-Hua Sun, Christine Simpson, Changqing Zhang, Karl Insogna
Breast cancer-associated gene 3 (BCA3) is a recently identified adaptor protein whose functions are still being defined. BCA3 has been reported to be an important regulator of nuclear factor-κB (NF-κB) signaling. It has also been reported to interact with the small GTPase, Rac1. Consistent with that observation, in the present study, BCA3 was found to interact with nuclear Rac1 in 293 cells and influence NF-κB signaling. Additional experiments revealed that depending on cell type, BCA3 augmented, attenuated or had no effect on NF-κB signaling in vitro...
August 4, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28780081/grb7-is-over-expressed-in-cervical-cancer-and-facilitate-invasion-and-inhibit-apoptosis-in-cervical-cancer-cells
#5
Hong-Bing Zhao, Xi-Feng Zhang, Xue-Lin Jia, Hao-Bin Wang
Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling. The objective of this study was to investigate the expression of Grb7 and its clinicopathological significance in cervical cancer. Utilising immunohistochemical staining, we examined the expression of Grb7 in 120 cases of human cervical cancer tissue and 10 cases of adjacent non-cancerous cervical tissue. The positive rate of Grb7 protein expression was 34...
July 26, 2017: Pathology, Research and Practice
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
#6
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/28759530/sevoflurane-attenuates-systemic-inflammation-compared-with-propofol-but-does-not-modulate-neuro-inflammation-a-laboratory-rat-study
#7
Beatrice Beck-Schimmer, Lukas Baumann, Tanja Restin, Philipp Eugster, Melanie Hasler, Christa Booy, Martin Schläpfer
BACKGROUND: Septic encephalopathy is believed to be a result of neuro-inflammation possibly triggered by endotoxins, such as lipopolysaccharides (LPS). Modulation of the immune system is a property of volatile anaesthetics. OBJECTIVE: We aimed to investigate the systemic and cerebral inflammatory response in a LPS-induced sepsis model in rats. We compared two different sedation strategies, intravenous propofol and the volatile anaesthetic sevoflurane, with the hypothesis that the latter may attenuate neuro-inflammatory processes...
July 28, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28759024/malt1-promotes-melanoma-progression-through-jnk-c-jun-signaling
#8
Y Wang, G Zhang, J Jin, S Degan, Y Tameze, J Y Zhang
Mucosa-associated lymphoma antigen 1 (MALT1) is a lymphoma oncogene that regulates signal transduction as a paracaspase and an adaptor protein. Yet, the role of MALT1 in other solid cancers such as melanoma is not well-understood. Here, we demonstrate that MALT1 is overexpressed in malignant melanoma cells, and predicts a poor disease-free survival. MALT1 inhibition via shRNA-mediated gene silencing or pharmacologically with MI-2 compound markedly reduced cell growth and migration of A2058 and A375 melanoma cell lines in vitro...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#9
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28740232/p62-sqstm1-sequestosome-1-is-an-n-recognin-of-the-n-end-rule-pathway-which-modulates-autophagosome-biogenesis
#10
Hyunjoo Cha-Molstad, Ji Eun Yu, Zhiwei Feng, Su Hyun Lee, Jung Gi Kim, Peng Yang, Bitnara Han, Ki Woon Sung, Young Dong Yoo, Joonsung Hwang, Terry McGuire, Sang Mi Shim, Hyun Dong Song, Srinivasrao Ganipisetti, Nuozhou Wang, Jun Min Jang, Min Jae Lee, Seung Jun Kim, Kyung Ho Lee, Jin Tae Hong, Aaron Ciechanover, Inhee Mook-Jung, Kwang Pyo Kim, Xiang-Qun Xie, Yong Tae Kwon, Bo Yeon Kim
Macroautophagy mediates the selective degradation of proteins and non-proteinaceous cellular constituents. Here, we show that the N-end rule pathway modulates macroautophagy. In this mechanism, the autophagic adapter p62/SQSTM1/Sequestosome-1 is an N-recognin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg). Both types of N-degrons bind its ZZ domain. By employing three-dimensional modeling, we developed synthetic ligands to p62 ZZ domain. The binding of Nt-Arg and synthetic ligands to ZZ domain facilitates disulfide bond-linked aggregation of p62 and p62 interaction with LC3, leading to the delivery of p62 and its cargoes to the autophagosome...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28734476/quantifying-the-interaction-between-egfr-dimers-and-grb2-in-live-cells
#11
Nuala Del Piccolo, Kalina Hristova
Adaptor proteins are a class of cytoplasmic proteins that bind to phosphorylated residues in receptor tyrosine kinases and trigger signaling cascades that control critically important cellular processes, such as cell survival, growth, differentiation, and motility. Here, we seek to characterize the interaction between epidermal growth factor receptor (EGFR) and the cytoplasmic adaptor protein growth factor receptor-bound protein 2 (Grb2) in a cellular context. To do so, we explore the utility of a highly biologically relevant model system, mammalian cells under reversible osmotic stress, and a recently introduced Förster resonance energy transfer microscopy method, fully quantified spectral imaging...
July 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28730277/regulation-of-class-v-myosin
#12
REVIEW
Ning Zhang, Lin-Lin Yao, Xiang-Dong Li
Class V myosin (myosin-5) is a molecular motor that functions as an organelle transporter. The activation of myosin-5's motor function has long been known to be associated with a transition from the folded conformation in the off-state to the extended conformation in the on-state, but only recently have we begun to understand the underlying mechanism. The globular tail domain (GTD) of myosin-5 has been identified as the inhibitory domain and has recently been shown to function as a dimer in regulating the motor function...
July 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28727291/proteomic-analysis-and-bioluminescent-reporter-gene-assays-to-investigate-effects-of-simulated-microgravity-on-caco-2-cells
#13
Giorgia La Barbera, Anna Laura Capriotti, Elisa Michelini, Susy Piovesana, Maria Maddalena Calabretta, Riccardo Zenezini Chiozzi, Aldo Roda, Aldo Laganà
Microgravity is one of the most important features in spaceflight. Previous evidence from in-vitro studies has shown that significant changes occur under simulated microgravity. For this reason, human colon adenocarcinoma Caco-2 cells were selected as cell model of intestinal epithelial barrier and their response to altered gravity conditions was investigated, especially on the protein level. In this study, we combined label-free shotgun proteomics and bioluminescent reporter gene assays to identify key proteins and pathways involved in the response of Caco-2 cells under reference and microgravity conditions...
July 20, 2017: Proteomics
https://www.readbyqxmd.com/read/28724756/lysosomal-targeting-of-sidt2-via-multiple-yxx%C3%AE-motifs-is-required-for-sidt2-function-in-the-process-of-rnautophagy
#14
Viorica Raluca Contu, Katsunori Hase, Hiroko Kozuka-Hata, Masaaki Oyama, Yuuki Fujiwara, Chihana Kabuta, Masayuki Takahashi, Fumihiko Hakuno, Shin-Ichiro Takahashi, Keiji Wada, Tomohiro Kabuta
RNA degradation is an essential process for maintaining cellular homeostasis. Previously, we have discovered a novel RNA degradation system, RNautophagy, during which direct import of RNA into lysosomes in an ATP-dependent manner followed by degradation takes place. The putative nucleic acids transporter, SID-1 transmembrane family member 2 (SIDT2), predominantly localizes to lysosomes and mediates the translocation of RNA into lysosomes during RNautophagy. However, little is known about the mechanisms of sorting SIDT2 to lysosomes...
July 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28724634/adaptor-protein-p62-promotes-skin-tumor-growth-and-metastasis-and-is-induced-by-uva-radiation
#15
Ashley Sample, Baozhong Zhao, Lei Qiang, Yu-Ying He
Skin cancer is the most common cancer and exposure to ultraviolet (UV) radiation, namely UVA and UVB is the major risk factor for skin cancer development. UVA is significantly less effective in causing direct DNA damage than UVB, but UVA has been shown to increase skin cancer risk. The mechanism by which UVA contributes to skin cancer remains unclear. Here, using RNA-Seq, we show that UVA induces autophagy and lysosomal gene expression, including the autophagy receptor and substrate p62. We found that UVA activates the transcription factor EB (TFEB), a known regulator of autophagy and lysosomal gene expression, which, in turn, induces p62 transcription...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724435/ww-domain-binding-protein-2-an-adaptor-protein-closely-linked-to-the-development-of-breast-cancer
#16
REVIEW
Shuai Chen, Han Wang, Yu-Fan Huang, Ming-Li Li, Jiang-Hong Cheng, Peng Hu, Chuan-Hui Lu, Ya Zhang, Na Liu, Chi-Meng Tzeng, Zhi-Ming Zhang
The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#17
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28713858/life-stage-specific-cargo-receptors-facilitate-glycosylphosphatidylinositol-anchored-surface-coat-protein-transport-in-trypanosoma-brucei
#18
Emilia K Kruzel, George P Zimmett, James D Bangs
The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level...
July 2017: MSphere
https://www.readbyqxmd.com/read/28712573/ve-cadherin-phosphorylation-regulates-endothelial-fluid-shear-stress-responses-through-the-polarity-protein-lgn
#19
Daniel E Conway, Brian G Coon, Madhusuthan Budatha, Paul T Arsenovic, Fabrizio Orsenigo, Florian Wessel, Jiasheng Zhang, Zhenwu Zhuang, Elisabetta Dejana, Dietmar Vestweber, Martin A Schwartz
Fluid shear stress due to blood flow on the vascular endothelium regulates blood vessel development, remodeling, physiology, and pathology [1, 2]. A complex consisting of PECAM-1, VE-cadherin, and vascular endothelial growth factor receptors (VEGFRs) that resides at endothelial cell-cell junctions transduces signals important for flow-dependent vasodilation, blood vessel remodeling, and atherosclerosis. PECAM-1 transduces forces to activate src family kinases (SFKs), which phosphorylate and transactivate VEGFRs [3-5]...
July 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28703133/association-of-autoimmune-hepatitis-with-src-homology-2-adaptor-protein-3-gene-polymorphisms-in-japanese-patients
#20
Takeji Umemura, Satoru Joshita, Hideaki Hamano, Kaname Yoshizawa, Shigeyuki Kawa, Eiji Tanaka, Masao Ota
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized by an autoimmune reaction to hepatocytes. The Src homology 2 adaptor protein 3 (SH2B3) gene is a member of the SH2B family of adaptor proteins that has been implicated in the integration and regulation of multiple signaling events. SH2B3 is involved in cytokine signaling pathways and serves as a negative mediator of T-cell receptor signaling. Genome-wide association analyses in Caucasians have linked a missense mutation at rs3184504 in SH2B3 with AIH...
July 13, 2017: Journal of Human Genetics
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