The actin/MKL1 signaling pathway influences cell growth and gene expression through large-scale chromatin reorganization and histone post-translational modifications
This study provides the first evidence for a global, reversible hetero/euchromatinization phenomenon triggered by the actin/MKL1 signaling pathway. (Source: BJ Cell)
Source: BJ Cell - April 24, 2014 Category: Biochemistry Authors: G Flouriot, G Huet, F Demay, F Pakdel, N Boujrad, D Michel Tags: BJ Cell Source Type: research
Drp1 stabilizes p53 on the mitochondria to trigger necrosis under oxidative stress conditions, in vitro and in vivo
In this study, we showed that Dynamin-related protein 1 (Drp1), a primary mitochondrial fission protein, stabilizes the well-known stress gene p53 and is required for p53 translocation to the mitochondria under conditions of oxidative stress. We found that Drp1 binding to p53 induced mitochondria-related necrosis. In contrast, inhibition of Drp1 hyperactivation by Drp1 silence RNA reduced necrotic cell death in cell culture exposed to oxidative stress. Most significantly, we demonstrated that inhibition of Drp1 by the Drp1 peptide inhibitor P110, which was recently developed by our group, abolished p53 association with the...
Source: BJ Cell - April 23, 2014 Category: Biochemistry Authors: X Guo, H Sesaki, X Qi Tags: BJ Signal Source Type: research
Inactivation of Mammalian Ero1{alpha} is catalysed by Specific Protein Disulfide Isomerases
Disulfide formation within the endoplasmic reticulum is a complex process requiring a disulfide exchange protein such as protein disulfide isomerase and a mechanism to form disulfides de novo. In mammalian cells, the major pathway for de novo disulfide formation involves the enzyme Ero1α which couples oxidation of thiols to the reduction of molecular oxygen to form hydrogen peroxide. Ero1α activity is tightly regulated by a mechanism that requires the formation of regulatory disulfides. These regulatory disulfides are reduced to activate and reform to inactive the enzyme. To investigate the mechanism of inact...
Source: BJ Cell - April 23, 2014 Category: Biochemistry Authors: C Shepherd, O B.V. Oka, N J. Bulleid Tags: BJ Biomolecules Source Type: research
Genetic ablation of plasmoDJ1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production
Malaria parasites must respond to stresses and environmental signals to perpetuate efficiently during their multi-stage development in diverse environments. To gain insights into the parasite’s stress response mechanisms, we investigated a conserved Plasmodium protein, which we have named plasmoDJ1 based on the presence of a putative cysteine protease motif of the DJ-1/PfpI superfamily, for its activities, potential to respond to stresses, and role in parasite development. PlasmoDJ1 is expressed in all intraerythrocytic stages and ookinetes. Its expression was increased 7-9 times upon heat shock and oxidative stress...
Source: BJ Cell - April 23, 2014 Category: Biochemistry Authors: N Singhal, A ., B S Mastan, K Arun Kumar, P Singh Sijwali Tags: BJ Cell Source Type: research
Sea anemone toxin AdE-1 modifies both sodium and potassium currents of rat cardiomyocytes
AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids with a molecular weight of 4907D. It was previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins, enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation. However, it did not induce spontaneous twitches. AdE-1 increased the duration of the cardiomyocyte action potential and decreased its amplitude and its time-to-peak in a concentration-dependent manner without affecting its threshold and cell resting potential. Nor did it generate the early and delayed after-...
Source: BJ Cell - April 22, 2014 Category: Biochemistry Authors: N Nesher, E Zlotkin, B Hochner Tags: BJ ChemBio Source Type: research
A Fab fragment directed against the neural cell adhesion molecule L1 enhances functional recovery after injury of the adult mouse spinal cord
Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery, which leads to severe disabilities in motor functions or pain. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration. Here, we describe the cloning, functional expression in E. coli and purification of a recombinant αL1 Fab fragment that binds to L1 with comparable activity as the function-triggering monoclonal antibody 557 and induces neurite outgrowth and neuronal survival...
Source: BJ Cell - March 27, 2014 Category: Biochemistry Authors: G Loers, Y Cui, I Neumaier, M Schachner, A Skerra Tags: BJ Biomolecules Source Type: research
Roundabout 1 exists predominantly as a basal dimeric complex and this is unaffected by binding of the ligand Slit2
Roundabout (Robo) receptors and their Slit polypeptide ligands are known to play key roles in neuronal development and have been implicated in both angiogenesis and cancer development. Like the other family members Robo1 is a large, single transmembrane domain, polypeptide containing a series of well defined extracellular elements. However, the intracellular domain lacks structural definition and little is known about the quaternary structure of Robo receptors or how binding of a Slit might affect this. To address these questions combinations of both autofluorescent protein-based FRET imaging and time-resolved FRET were em...
Source: BJ Cell - March 27, 2014 Category: Biochemistry Authors: L Zakrys, R J Ward, J D. Pediani, A G Godin, G J Graham, G Milligan Tags: BJ Biomolecules Source Type: research
T-cell co-stimulation through the CD2 and CD28 co-receptors induces distinct signaling responses
In conclusion, CD2 and CD28 co-stimulation induce distinct signaling responses and functional outcomes in T cells. (Source: BJ Cell)
Source: BJ Cell - March 25, 2014 Category: Biochemistry Authors: S S. Skånland, K Moltu, T Berge, E M. Aandahl, K Taskén Tags: BJ Signal Source Type: research
Trafficking modulator TENin1 inhibits endocytosis, causes endomembrane protein accumulation at the pre-vacuolar compartment and impairs gravitropic response in Arabidopsis thaliana
This study characterises an inhibitor of endomembrane protein trafficking, Trafficking & ENdocytosis inhibitor 1, TENin1 (TE1) that reduces gravitropic root bending in Arabidopsis thaliana seedlings. Short term TE1 treatment causes accumulation of plasma membrane (PM) proteins including brassinosteroid receptor BRI1, plasma membrane intrinsic protein 2a (PIP2a) and auxin transporter PIN-FORMED 2 (PIN2) in a pre-vacuolar related compartment (PVC), which is sensitive to Brefeldin A (BFA). This compound inhibits endocytosis from the PM, and promotes trafficking to the vacuole, consistent with inhibition of retrieval of protei...
Source: BJ Cell - March 21, 2014 Category: Biochemistry Authors: R Paudyal, A Jamaluddin, J P Warren, S M. Doyle, S Robert, S L. Warriner, A Baker Tags: BJ Plant Source Type: research
TIMP-1 Modulates Chemotaxis of Human Neural Stem Cells Through CD63 and Integrin Signaling
In this study, we used microarray and proteomics analyses to identify a novel chemoattractant molecule, tissue inhibitor of metalloproteinase-1 (TIMP-1), secreted from human brain tumor tissues. We demonstrate that TIMP-1 significantly enhances hNSC adhesion and migration in a cell culture system. These effects were critically dependent on CD63, as short hairpin RNA-mediated ablation of CD63 expression attenuated the response. TIMP-1 significantly increased the number of focal adhesions (FAs) and cytoskeletal reorganization for cell migration in hNSCs, whereas knockdown of CD63 resulted in decreased hNSC spreading, FAs, an...
Source: BJ Cell - March 18, 2014 Category: Biochemistry Authors: S Lee, J Kim, S Cho, H Kim, H Shin, J Jeon, R Kausar, S Jeong, Y Lee, M Lee Tags: BJ Cell Source Type: research
Analysis of the Leishmania Peroxin 7 Interactions with Peroxin 5, Peroxin 14 and PTS2 Ligands
The Leishmania receptorperoxin PEX7 (LPEX7) is essential for targeting newly synthesized proteins with a PTS2 import signal into the glycosome. Here we describe the biophysical characterization of a functional LPEX7 isolated from E. coli inclusion bodies. Pull down assays showed that this LPEX7 binds the interacting partners LdPEX5 and LdPEX14, but more importantly, this receptor can specifically binds PTS2 cargo proteins in the monomeric and dimeric state. However, in the absence of interacting partners LPEX7 preferentially adopts a tetrameric structure. Mapping studies localized the LdPEX5 and LdPEX14 binding sites to th...
Source: BJ Cell - March 18, 2014 Category: Biochemistry Authors: A Victora Pilar, R Strasser, J McLean, E Quinn, N Cyr, H Hojjat, A Hasil Kottarampatel, A Jardim Tags: BJ Biomolecules Source Type: research
The interaction with caveolae-associated proteins regulates enolase-1 subcellular localization
Cell surface-associated proteolysis plays a crucial role in embryonic development, monocyte/macrophage recruitment and tumor cell invasion. The glycolytic enzyme enolase-1 (ENO-1) is translocated from the cytoplasm to the cell surface, where it binds plasminogen (PLG) to enhance pericellular plasmin production and cell motility. In our study, ENO-1 was found to localize to a specialized subset of lipid rafts called caveolae as demonstrated by fluorescence confocal microscopy and sucrose gradient ultracentrifugation. Co-immunoprecipitation studies revealed that ENO-1 interacts with caveolin (Cav)-1, but not with Cav-2, via ...
Source: BJ Cell - March 14, 2014 Category: Biochemistry Authors: D Zakrzewicz, M Didiasova, A Zakrzewicz, A C. Hocke, F Uhle, P Markart, K T. Preissner, M Wygrecka Tags: BJ Cell Source Type: research
Novel Role of a Family of Major Facilitator Transporters in Biofilm Development and Virulence of Candida albicans
The Quinidine Drug Resistance (QDR) family of genes encodes transporters belonging to the Major Facilitator Superfamily (MFS) of proteins. We show that, QDR transporters, which are localized to the plasma membrane, do not play a role in drug transport. Hence, null mutants of QDR1, QDR2 and QDR3 display no alterations in susceptibility to azoles, polyenes, echinocandins, polyamines or quinolines, or to cell wall inhibitors and many other stresses. However, the deletion of QDR genes, individually or collectively, led to defects in biofilm architecture and thickness. Interestingly, QDR-lacking strains also displayed attenuate...
Source: BJ Cell - March 13, 2014 Category: Biochemistry Authors: A Haseeb Shah, A Singh, S Dhamgaye, N Chauhan, P Vandeputte, K Jyothiraj Suneetha, R Kaur, P K. Mukherjee, J Chandra, M A. Ghannoum, D Sanglard, S K. Goswami, R Prasad Tags: BJ Cell Source Type: research
Three conserved histidyl residues contribute to mitochondrial iron transport through mitoferrins
Iron is an essential element for almost all organisms. In eukaryotes, it is mainly used in mitochondria for the biosynthesis of iron-sulphur clusters and heme-group maturation. Iron is delivered into the mitochondrion by mitoferrins, members of the mitochondrial carrier family (MCF), through an unknown mechanism. In this article, the yeast homologs of these proteins, Mrs3p and Mrs4p, were studied by inserting them into liposomes. In this context, they could transport iron (II) across the proteoliposomes membrane, as revealed using the iron-chelator bathophenanthroline. A series of amino acid-modifying reagents were screene...
Source: BJ Cell - March 13, 2014 Category: Biochemistry Authors: X Brazzolotto, F Pierrel, L Pelosi Tags: BJ Energy Source Type: research
MiR-30b regulates migration and invasion of human colorectal cancer via SIX1
Colorectal cancer (CRC) is one of the most malignant tumors in both developing and developed countries. It is estimated that 60% of CRC patients bear liver metastasis. Here, we revealed that miR-30b is an important regulator in human CRC liver metastasismigration and invasion which are vital steps in CRC liver metastasis of human CRCs. MiR-30b was significantly downregulated in primary CRC specimens compared with normal tissues. Furthermore, miR-30b was much lower in liver metastasis (LM) tissues than in CRCs. We validated SIX1, a member of the six-homeodomain family of transcription factorsand an EMT (epithelial-to-mesenc...
Source: BJ Cell - March 5, 2014 Category: Biochemistry Authors: H Zhao, Z Xu, H Qin, Z Gao, L Gao Tags: BJ Cell Source Type: research
