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Adaptor protein 1

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https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#1
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28427457/integrative-modelling-of-tir-domain-containing-adaptor-molecule-inducing-interferon-%C3%AE-trif-provides-insights-into-its-autoinhibited-state
#2
Jarjapu Mahita, Ramanathan Sowdhamini
BACKGROUND: TRIF is a key protein in antiviral innate immunity, operating downstream of TLRs. TRIF activation leads to the production of interferon-β and pro-inflammatory cytokines. There is evidence from experiments to suggest that the N-terminal domain of TRIF binds to its TIR domain to avoid constitutive activation. However, no structure of a complex between the N-terminal domain and the TIR domain exists till date. The disordered nature of the region connecting the N-terminal domain and the TIR domain compounds the issue of elucidating the mechanism of autoinhibition of TRIF...
April 20, 2017: Biology Direct
https://www.readbyqxmd.com/read/28424516/slamf7-is-critical-for-phagocytosis-of-haematopoietic-tumour-cells-via-mac-1-integrin
#3
Jun Chen, Ming-Chao Zhong, Huaijian Guo, Dominique Davidson, Sabrin Mishel, Yan Lu, Inmoo Rhee, Luis-Alberto Pérez-Quintero, Shaohua Zhang, Mario-Ernesto Cruz-Munoz, Ning Wu, Donald C Vinh, Meenal Sinha, Virginie Calderon, Clifford A Lowell, Jayne S Danska, André Veillette
Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer...
April 19, 2017: Nature
https://www.readbyqxmd.com/read/28418930/the-innate-immunity-of-guinea-pigs-against-highly-pathogenic-avian-influenza-virus-infection
#4
Kun Zhang, Wei Wei Xu, Zhaowei Zhang, Jing Liu, Jing Li, Lijuan Sun, Weiyang Sun, Peirong Jiao, Xiaoyu Sang, Zhiguang Ren, Zhijun Yu, Yuanguo Li, Na Feng, Tiecheng Wang, Hualei Wang, Songtao Yang, Yongkun Zhao, Xuemei Zhang, Peter R Wilker, WenJun Liu, Ming Liao, Hualan Chen, Yuwei Gao, Xianzhu Xia
H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418088/rack1-forms-a-complex-with-fgfr1-and-pkm2-and-stimulates-the-growth-and-migration-of-squamous-lung-cancer-cells
#5
Chengzhi Zhou, Tao Chen, Zhanhong Xie, Yinyin Qin, Yangming Ou, Jiexia Zhang, Shiyue Li, Rongchang Chen, Nanshan Zhong
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over-expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28416805/a-new-inhibitor-of-the-%C3%AE-arrestin-ap2-endocytic-complex-reveals-interplay-between-gpcr-internalization-and-signalling
#6
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28414818/tgf%C3%AE-smad3-regulates-proliferation-and-apoptosis-through-irs-1-inhibition-in-colon-cancer-cells
#7
Katie L Bailey, Ekta Agarwal, Sanjib Chowdhury, Jiangtao Luo, Michael G Brattain, Jennifer D Black, Jing Wang
In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation of TGFβ activation leads to elevated expression and phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell proliferation, decreased apoptosis and increased tumor growth in vitro and in vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated oncogenic phenotypes, indicating that TGFβ/Smad3 signaling inhibits cell proliferation and increases apoptosis at least partially through the inhibition of IRS-1 expression and activation...
2017: PloS One
https://www.readbyqxmd.com/read/28414306/targeting-prohibitins-with-chemical-ligands-inhibits-kras-mediated-lung-tumours
#8
H Yurugi, F Marini, C Weber, K David, Q Zhao, H Binder, L Désaubry, K Rajalingam
KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1 (PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF with PHB1 at the plasma membrane is essential for CRAF activation...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28410990/tyrosine-kinase-syk-licenses-myd88-adaptor-protein-to-instigate-il-1%C3%AE-mediated-inflammatory-disease
#9
Prajwal Gurung, Gaofeng Fan, John R Lukens, Peter Vogel, Nicholas K Tonks, Thirumala-Devi Kanneganti
Mice carrying a hypomorphic point mutation in the Ptpn6 gene (Ptpn6(spin) mice) develop an inflammatory skin disease that resembles neutrophilic dermatosis in humans. Here, we demonstrated that interleukin-1α (IL-1α) signaling through IL-1R and MyD88 in both stromal and immune cells drive inflammation in Ptpn6(spin) mice. We further identified SYK as a critical kinase that phosphorylates MyD88, promoted MyD88-dependent signaling and mediates dermatosis in Ptpn6(spin) mice. Our studies further demonstrated that SHP1 encoded by Ptpn6 binds and suppresses SYK activation to inhibit MyD88 phosphorylation...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28406398/lissencephaly-1-is%C3%A2-a-context-dependent-regulator%C3%A2-of-the-human-dynein-complex
#10
Janina Baumbach, Andal Murthy, Mark A McClintock, Carly I Dix, Ruta Zalyte, Ha Thi Hoang, Simon L Bullock
The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein and its accessory complex dynactin with dynamic microtubule plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein-1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus end-directed human dynein complexes with these sites. LIS1 promotes dynactin-dependent tracking of dynein on both growing and shrinking plus ends...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28393246/the-downstream-of-tyrosine-kinase-7-is-reduced-in-lung-cancer-and-is-associated-with-poor-survival-of-patients-with-lung-cancer
#11
Gang Chen, Hefen Yu, Lucy Satherley, Catherine Zabkiewicz, Jeyna Resaul, Huishan Zhao, Hu Mu, Xiuyi Zhi, Junqi He, Lin Ye, Wen G Jiang
The downstream of tyrosine kinase 7 (DOK7) is an adaptor protein mediating signalling transduction between receptors and intracellular downstream molecules. Reduced expression of DOK7 has been observed in breast cancer. The present study aimed to investigate the role played by DOK7 in lung cancer. The expression of DOK7 at both mRNA and protein levels was evaluated in human lung cancer. A reduced expression of DOK7 transcripts was seen in lung cancers compared with normal lung tissues. Kaplan-Meier analyses showed that the reduced expression of DOK7 was associated with poorer overall survival and progression-free survival of patients with lung cancer...
March 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28389649/recombinant-slit2-reduces-surgical-brain-injury-induced-blood-brain-barrier-disruption-via-robo4-dependent-rac1-activation-in-a-rodent-model
#12
Prativa Sherchan, Lei Huang, Onat Akyol, Cesar Reis, Jiping Tang, John H Zhang
Brain tissue surrounding surgical resection site can be injured inadvertently due to procedures such as incision, retractor stretch, and electrocauterization when performing neurosurgical procedures, which is termed as surgical brain injury (SBI). Blood brain barrier (BBB) disruption due to SBI can exacerbate brain edema in the post-operative period. Previous studies showed that Slit2 exhibited vascular anti-permeability effects outside the brain. However, BBB protective effects of Slit2 following SBI has not been evaluated...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389644/assembly-of-ruminococcus-flavefaciens-cellulosome-revealed-by-structures-of-two-cohesin-dockerin-complexes
#13
Pedro Bule, Victor D Alves, Vered Israeli-Ruimy, Ana L Carvalho, Luís M A Ferreira, Steven P Smith, Harry J Gilbert, Shabir Najmudin, Edward A Bayer, Carlos M G A Fontes
Cellulosomes are sophisticated multi-enzymatic nanomachines produced by anaerobes to effectively deconstruct plant structural carbohydrates. Cellulosome assembly involves the binding of enzyme-borne dockerins (Doc) to repeated cohesin (Coh) modules located in a non-catalytic scaffoldin. Docs appended to cellulosomal enzymes generally present two similar Coh-binding interfaces supporting a dual-binding mode, which may confer increased positional adjustment of the different complex components. Ruminococcus flavefaciens' cellulosome is assembled from a repertoire of 223 Doc-containing proteins classified into 6 groups...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389259/autophagy-induction-by-celastrol-augments-protection-against-bleomycin-induced-experimental-pulmonary-fibrosis-in-rats-role-of-adaptor-protein-p62-sqstm1
#14
Thomas Divya, Anandasadagopan Sureshkumar, Ganapasam Sudhandiran
Pulmonary fibrosis (PF) is a chronic pulmonary disease of unknown cause with high mortality. Autophagy is an important homeostatic process that decides the fate of cells under stress conditions. This study is aimed to investigate whether impaired autophagic activity leads to fibrosis and pharmacological induction of autophagy provides protection against bleomycin (BLM)-induced PF. A single dose of BLM (3 U/kg body weight) was administered intratracheally to induce fibrosis in rats. Celastrol, a triterpenoid (5 mg/kg/body weight, intraperitoneally) was given in every 81 h for a period of 28 days...
April 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28384159/3lps-binding-protein-and-its-interactions-with-p-gingivalis-lps-modulate-pro-inflammatory-response-and-toll-like-receptor-signaling-in-human-oral-keratinocytes
#15
Pei-Hui Ding, Richard P Darveau, Cun-Yu Wang, Lijian Jin
Lipopolysaccharide (LPS)-binding protein (LBP) as an acute-phase protein plays a crucial role in innate host response to bacterial challenge. Our previous study shows that LBP expression in human gingiva is associated with periodontal status. Porphyromonas gingivalis is a keystone periodontopathogen, and its LPS with lipid A structural heterogeneity critically accounts for periodontal pathogenesis. This study investigated the effects of LBP and its interactions with two featured isoforms of P. gingivalis LPS (tetra-acylated LPS1435/1449 and penta-acylated LPS1690) on the expression of pro-inflammatory cytokines in human oral keratinocytes (HOKs), and the involvement of Toll-like receptor (TLR) signaling...
2017: PloS One
https://www.readbyqxmd.com/read/28381567/the-cbl-e3-ligase-mediates-the-removal-of-nectin-1-from-the-surface-of-the-herpes-simplex-virus-type-1-infected-cells
#16
Thibaut Deschamps, Christos Dogrammatzis, Ranajoy Mullick, Maria Kalamvoki
The Cbl E3 ligase has been linked to the down-modulation of surface signaling responses by inducing internalization of surface receptors. The adaptor protein CIN85 is a partner of Cbl that augments many of these interactions. Previously, an interaction was demonstrated between ICP0 and CIN85, which results in the removal of EGFR from the surface of the infected cells with a concomitant attenuation of EGFR signaling. Here, we examined whether Cbl mediates the removal of the herpes simplex virus 1 (HSV-1) entry receptor Nectin-1 from the surface of infected cells...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28381552/the-structure-and-polymerase-recognition-mechanism-of-the-crucial-adaptor-protein-and-1-in-the-human-replisome
#17
Chengcheng Guan, Jun Li, Dapeng Sun, Yingfang Liu, Huanhuan Liang
DNA replication in eukaryotic cells is performed by a multi-protein complex called the replisome, which consists of helicases, polymerases and adaptor molecules. Human acidic nucleoplasmic DNA-binding protein 1 (AND-1), also known as WD repeat and HMG-box DNA binding protein 1 (WDHD1), is an adaptor molecule crucial for DNA replication. While structural information for the AND-1 yeast ortholog is available, the mechanistic details for how human AND-1 protein anchors the lagging-strand DNA polymerase α (Pol α) to the DNA helicase complex (Cdc45-MCM2-7-GINS, CMG) await elucidation...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28381191/expression-and-associations-of-traf1-bmi-1-aldh1-and-lin28b-in-oral-squamous-cell-carcinoma
#18
Tian-Fu Wu, Yi-Cun Li, Si-Rui Ma, Bing-Liu, Wen-Feng Zhang, Zhi-Jun Sun
Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28377308/cell-type-specific-regulatory-effects-of-glucocorticoids-on-cutaneous-tlr2-expression-and-signalling
#19
Qi Su, Anja Pfalzgraff, Günther Weindl
Glucocorticoids (GCs) induce Toll-like receptor (TLR) 2 expression and synergistically upregulate TLR2 with pro-inflammatory cytokines or bacteria. These paradoxical effects have drawn attention to the inflammatory initiating or promoting effects of GCs, as GC treatment can provoke inflammatory skin diseases. Here, we aimed to investigate the regulatory effects of GCs in human skin cells of different epidermal and dermal layers. We found that Dex induced TLR2 expression mainly in undifferentiated and less in calcium-induced differentiated keratinocytes but not in HaCaT cells or fibroblasts, however, Dex reduced TLR1/6 expression...
April 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28375585/down-regulation-of-talin1-promotes-hepatocellular-carcinoma-progression-via-activation-of-the-erk1-2-pathway
#20
Chen Peijuan, Lei Ling, Wang Jian, Zou Xuejing, Zhang Dongyan, Deng Ling, Wu Dehua
Talin1 is an adaptor protein that conjugates integrins to the cytoskeleton and regulates integrins and focal adhesion signaling. Several studies have found that Talin1 is over-expressed in several tumor types and promotes tumor progression. However, the explicit role of Talin1 in hepatocellular carcinoma (HCC) progression is still unclear and its functional mechanism remains largely unknown. In this study, we showed a trend of gradually decreasing expression of Talin1 from normal liver tissues to hepatocirrhosis, liver hyperplasia, the corresponding adjacent non-tumor, primary HCC and eventually metastatic foci, indicating that Talin1 maybe correlate with HCC initiation to progression...
April 4, 2017: Cancer Science
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