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Yafang Chen, Junhui Sui, Qing Wang, Yijia Yin, Jun Liu, Qiguang Wang, Xianglong Han, Yong Sun, Yujiang Fan, Xingdong Zhang
The injectable self-crosslinking blend hydrogel by combination of collagen I and thiolated hyaluronic acid could alleviate collagen I contraction in vitro and overcome weak cell adhesive sites of hyaluronic acid. Five groups of injectable hydrogels with different ratios were prepared to investigate their gelation time, injection force, mechanical properties, swelling capacity and disintegration performance. These results indicated that Col7 HA-SH3 hydrogel achieved the optimal controlled and injectable effect, the gelation time was just ten seconds with injection force at 3...
June 15, 2018: Carbohydrate Polymers
Jaechul Yoon, Dohern Kym, Jun Hur, Youngmin Kim, Hyeong-Tae Yang, Haejun Yim, Yong Suk Cho, Wook Chun
OBJECTIVES: We evaluated the ability of new sepsis (S3) criteria (compared with previous definitions of sepsis [S1] and burn sepsis criteria) to accurately determine the mortality in severe burns patients with sepsis. DESIGN: This was retrospective cohort study. SETTING: The Burn ICU of Burn Center, Hangang Sacred Heart Hospital, Hallym University, Seoul, Korea. PATIENTS: A total of 1,185 adult patients (mean age, 49...
April 3, 2018: Critical Care Medicine
Hongjuan You, Fanyun Kong, Kai Zhou, Xiao Wei, Lei Hu, Wei Hu, Wenya Luo, Yanbo Kou, Xiaomei Liu, Xi Chen, Kuiyang Zheng, Renxian Tang
LIM and SH3 domain protein 1 (LASP-1) is known to participate in the progression of hepatocellular carcinoma (HCC). We previously showed that ectopic expression of hepatitis B virus (HBV) X protein (HBX) enhanced the expression of LASP-1, which promoted proliferation and migration of HCC cells. Here, we further demonstrated the molecular mechanism underlying upregulation of LASP-1, mediated by HBX, in HBV-infected HCC cells. Through a luciferase activity assay, we discovered that the LASP-1 promoter region regulated by HBX contained an AP-1 binding element in human hepatoma cells...
March 30, 2018: Journal of Cellular Physiology
Gualtiero Alvisi, Lucia Paolini, Andrea Contarini, Chiara Zambarda, Veronica Di Antonio, Antonella Colosini, Nicole Mercandelli, Martina Timmoneri, Giorgio Palù, Luigi Caimi, Doris Ricotta, Annalisa Radeghieri
Intersectin 1-short (ITSN1-s) is a 1220 amino acids ubiquitously-expressed scaffold protein presenting a multi-domain structure that allows to spatiotemporally regulate the functional interaction of a plethora of proteins. Beside its well-established role in endocytosis, ITSN1-s is involved in regulation of cell signaling and is implicated in tumorigenesis processes, although the signaling pathways involved are still poorly understood. Here we identify ITSN1-s as a nucleocytoplasmic trafficking protein. We show that, by binding to importin (IMP)a, a small fraction of ITSN1-s localizes in the cell nucleus at the steady state, where it preferentially associates with the nuclear envelope (NE) and interacts with lamin A/C...
March 29, 2018: Biochemical Journal
Qingxia Li, Wanfa Yang, Yue Wang, Wei Liu
Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 (ARAP1), Cbl-interacting protein of 85 kDa (CIN85), and casitas B-lineage lymphoma (Cbl) play important roles in epidermal growth factor receptor (EGFR) internalization and recycling. In previous studies, ARAP1 was found to interact with CIN85, and their interaction attenuated the ubiquitination of EGFR. However, the molecular mechanism was still unclear. In this study, we first biochemically and structurally characterized the interaction between ARAP1 and CIN85, and found that the CIN85 SH3B domain bound to the ARAP1 PXPXXRX (except P) XXR/H/K motif with high affinity and specificity...
March 28, 2018: Biochemistry
Joon Haeng Hur, Sang-Hee Lee, A-Young Kim, Young Ho Koh
Nervous wreck (Nwk), a protein that is present at Type 1 glutamatergic synapses that contains an SH3 domain and an FCH motif, is a Drosophila homolog of the human srGAP3/MEGAP protein, which is associated with mental retardation. Confocal microscopy revealed that circles in Nwk reticulum enclosed T-shaped active zones (T-AZs) and partially colocalized with synaptic vesicle (SV) markers and both exocytosis and endocytosis components. Results from an electron microscopic (EM) analysis showed that Nwk proteins localized at synaptic edges and in SV pools...
March 23, 2018: Experimental & Molecular Medicine
Ze-Quan Mo, Qing Han, Yu-Long Zeng, Jiu-Le Wang, Xue-Zhu Li, Yan-Wei Li, Hong-Yan Sun, An-Xing Li, Xiao-Chun Luo, Xue-Ming Dan
Bruton's tyrosine kinase (BTK) is a Tec-family tyrosine kinase and plays a crucial role in B cell antigen receptor (BCR) signal pathway. Mutations in humans and mice BTK gene results in X-linked agammaglobulinemia (XLA) and X-linked immunodeficiency (XLD), respectively. To study the function of BTK in teleost, we cloned a BTK gene from orange-spotted grouper. Homology analysis showed that the grouper BTK (EcBTK) had a high amino acid identity with other vertebrates (63%-92%) and shared the highest amino acid identity with ballan wrasse Labrus bergylta BTK...
March 19, 2018: Fish & Shellfish Immunology
Linjie Zhao, Wei Wang, Shuang Huang, Zhengnan Yang, Lian Xu, Qilian Yang, Xiu Zhou, Jinjin Wang, Qiuhong Shen, Chenlu Wang, Xiaobing Le, Min Feng, Nianxin Zhou, Wayne Bond Lau, Bonnie Lau, Shaohua Yao, Tao Yi, Xin Wang, Xia Zhao, Yuquan Wei, Shengtao Zhou
BACKGROUND: Ovarian cancer constitutes one of the most lethal gynecologic malignancies for females. Currently, early detection strategies and therapeutic options for ovarian cancer are far from satisfactory, leading to high diagnosis rates at late stages and disease relapses. New avenues of therapy are needed that target key processes in ovarian cancer progression. While a variety of non-coding RNAs have been proven to regulate ovarian cancer metastatic progression, the functional roles of RNA-binding proteins (RBPs) in this process are less well defined...
March 16, 2018: Genome Biology
Tao Zhang, Guannan Zhao, Chuanhe Yang, Peixin Dong, Hidemichi Watari, Lin Zeng, Lawrence M Pfeffer, Junming Yue
Ovarian cancer is one of the most common malignancies in women and has a high mortality rate due to metastatic progression and tumor recurrence. ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is an ADP-ribosylation factor GTPase-activating protein, which is involved in tumor metastasis. However, the role of ASAP1 in ovarian cancer is completely unknown. The present study reported that ASAP1 was highly expressed in ovarian carcinoma, and expression positively-correlated with overall poor survival and prognosis of patients...
April 2018: Oncology Letters
Carmen Ruggiero, Mauro Grossi, Giorgia Fragassi, Antonella Di Campli, Carmine Di Ilio, Alberto Luini, Michele Sallese
Membrane trafficking via the Golgi-localised KDEL receptor activates signalling cascades that coordinate both trafficking and other cellular functions, including autophagy and extracellular matrix degradation. In this study, we provide evidence that membrane trafficking activates KDEL receptor and the Src family kinases at focal adhesions of HeLa cells, where this phosphorylates ADP-ribosylation factor GTPase-activating protein with SH3 domain, ankyrin repeat and PH domain (ASAP)1 and focal adhesion kinase (FAK)...
February 13, 2018: Oncotarget
Qingzu Gao, Lihua Tang, Ling Wu, Kaitao Li, Hui Wang, Weidong Li, Juan Wu, Mingyi Li, Shuang Wang, Liang Zhao
LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells...
March 12, 2018: Cell Death & Disease
Sandra Huber, Tulin Karagenc, Dominic Ritler, Sven Rottenberg, Kerry Woods
Theileria annulata is an apicomplexan parasite that modifies the phenotype of its host cell completely, inducing uncontrolled proliferation, resistance to apoptosis and increased invasiveness. The infected cell thus resembles a cancer cell, and changes to various host cell signaling pathways accompany transformation. Most of the molecular mechanisms leading to Theileria-induced immortalization of leukocytes remain unknown. The parasite dissolves the surrounding host cell membrane soon after invasion and starts interacting with host proteins, ensuring its propagation by stably associating with the host cell microtubule network...
March 8, 2018: Cellular Microbiology
Raji P Grewal, Kinsi Oberoi, Leema Reddy Peddareddygari
Charcot-Marie-Tooth disease type 4C, an autosomal recessive genetic neuropathy, is caused by mutations in the SH3TC2 (SH3 domain and tetratricopeptide repeats 2) gene. Interestingly, although mutations in this gene have been observed in European gypsies, a population that originated in India, there are few publications describing Indian patients. We report our analysis of a 50-year-old woman of Asian Indian descent with onset of progressive distal weakness and sensory loss in childhood. A clinical examination revealed the presence of a neuropathy with pes cavus without spinal abnormalities...
January 2018: Case Reports in Neurology
Pengfei Tian, John M Louis, James L Baber, Annie Aniana, Robert Best
Efficient and accurate models to predict the fitness of a sequence would be extremely valuable in protein design. We have explored the use of statistical potentials for the coevolutionary fitness landscape, extracted from known protein sequences, in conjuction with Monte Carlo simulations, as a tool for design. As proof of principle, we created a series of predicted high-fitness sequences for three different protein folds, representative of different structural classes: the GA (all-α) and GB (α/β) binding domains of streptococcal protein G, and an SH3 (all-β) domain...
March 7, 2018: Angewandte Chemie
Tzer Chyn Lim, Tomoyuki Hatano, Anton Kamnev, Mohan K Balasubramanian, Ting Gang Chew
The position of the division site dictates the size and fate of daughter cells in many organisms. In animal cells, division-site placement involves overlapping mechanisms, including signaling from the central spindle microtubules, astral microtubules, and spindle poles and through polar contractions [1-3]. In fission yeast, division-site positioning requires overlapping mechanisms involving the anillin-related protein Mid1 and the tip complex (comprising the Kelch-repeat protein Tea1, the Dyrk-kinase Pom1, and the SH3-domain protein Tea4) [4-11]...
February 22, 2018: Current Biology: CB
Lichun He, Sebastian Hiller
Many molecular chaperones are promiscuous and interact with a wide range of unfolded, quasi-native and native client proteins. Thereby, the mechanisms how chaperones interact with the highly diverse structures of native clients remain puzzling. In this work, we investigate at the atomic level how three ATP-independent chaperones interact with the β-sheet rich protein Fyn SH3 domain. The data reveal that the chaperone Spy recognizes the locally frustrated surface of the client SH3 and that the interaction is transient and highly dynamic, leaving the chaperone-interacting surface on SH3 solvent accessible...
March 2, 2018: Angewandte Chemie
Ksenia Krupina, Charlotte Kleiss, Sushil Awal, Irene Rodriguez-Hernandez, Victoria Sanz-Moreno, Izabela Sumara
Defects in mitosis can lead to aneuploidy, which is a common feature of human cancers. Spindle Assembly Checkpoint (SAC) controls fidelity of chromosome segregation in mitosis to prevent aneuploidy. The ubiquitin receptor protein Ubiquitin Associated and SH3 Domain Containing B (UBASH3B) was recently found to control SAC silencing and faithful chromosome segregation by relocalizing Aurora B kinase to the mitotic microtubules. Accordingly, loss and gain of function of UBASH3B have strong effects on mitotic progression...
2018: Molecular & Cellular Oncology
Shafqat Rasool, Naoto Soya, Luc Truong, Nathalie Croteau, Gergely L Lukacs, Jean-François Trempe
Mutations in PINK1 cause autosomal recessive Parkinson's disease (PD), a neurodegenerative movement disorder. PINK1 is a kinase that acts as a sensor of mitochondrial damage and initiates Parkin-mediated clearance of the damaged organelle. PINK1 phosphorylates Ser65 in both ubiquitin and the ubiquitin-like (Ubl) domain of Parkin, which stimulates its E3 ligase activity. Autophosphorylation of PINK1 is required for Parkin activation, but how this modulates the ubiquitin kinase activity is unclear. Here, we show that autophosphorylation of Tribolium castaneum PINK1 is required for substrate recognition...
February 23, 2018: EMBO Reports
Z Hu, X Wang, Y Cui, C Li, S Wang
The growing evidence shows that LIM and SH3 Domain Protein 1 (LASP1) is a multi-functional protein that plays important role in forming cytoskeleton and prognostic marker in different cancers. LASP1 expression is correlated with the grade, size, and the metastasis of tumor in clinical samples. And the upregulation of LASP1 facilitates tumor cells proliferation, migration, and invasion perhaps through the interaction with cytoskeleton and increased nuclear translocation. The underlying mechanism of LASP1 on tumor is still in the initial stage; therefore, the signaling pathways in various tumors are specifically summarized to deepen the biological understanding of LASP1...
February 21, 2018: Current Molecular Medicine
Srinivas Kumar Ponna, Salla Ruskamo, Matti Myllykoski, Corinna Keller, Tobias M Boeckers, Petri Kursula
The Shank proteins are crucial scaffolding elements of the post-synaptic density (PSD). One of the best-characterized domains in Shank is the PDZ domain, which binds to C-terminal segments of several other PSD proteins. We carried out a detailed structural analysis of Shank3 PDZ domain-peptide complexes, in order to understand determinants of binding affinity towards different ligand proteins. Ligand peptides from four different proteins were cocrystallized with the Shank3 PDZ domain, and binding affinities were determined calorimetrically...
February 23, 2018: Journal of Neurochemistry
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