Nrf2 impacts the efficiency of mitochondrial fatty acid oxidation
Transcription factor NF-E2 p45-related factor 2 (Nrf2) regulates the cellular redox homeostasis and cytoprotective responses, allowing adaptation and survival under conditions of stress. The significance of Nrf2 in intermediary metabolism is also beginning to be recognized. Thus, this transcription factor affects negatively fatty acid synthesis. However the effect of Nrf2 on fatty acid oxidation is presently unknown. We now report that the mitochondrial oxidation of long-(palmitic) and short-(hexanoic) chain fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively active. Addition of fatt...
Source: BJ Cell - November 8, 2013 Category: Biochemistry Authors: M H.R. Ludtmann, P R. Angelova, Y Zhang, A Y. Abramov, A T. Dinkova-Kostova Tags: BJ Metabolism Source Type: research
TRPML1 loss promotes production of reactive oxygen species: is oxidative damage a factor in mucolipidosis type IV?
TRPML1 is a lysosomal ion channel permeable to cations, including Fe2+. Mutations in MCOLN1, the gene coding for TRPML1, cause the lysosomal storage disease (LSD) Mucolipidosis type IV (MLIV). The role of TRPML1 in the cell is disputed and the mechanisms of cell deterioration in MLIV are unclear. The recent demonstration of Fe2+ buildup in MLIV cells raised the possibility that TRPML1 dissipates lysosomal Fe2+ and prevents its accumulation. Since Fe2+ catalyzes the production of reactive oxygen species (ROS), we set out to test whether or not the loss of TRPML1 promotes ROS production by Fe2�...
Source: BJ Cell - November 6, 2013 Category: Biochemistry Authors: J Coblentz, C St. Croix, K Kiselyov Tags: BJ Cell Source Type: research
Mammalian sterile 20-like kinase 1/2 inhibit Wnt/{beta}-catenin signaling pathway by directly binding Casein kinase 1 epsilon
In this study, using the tandem affinity purification and mass spectrometry analysis, CK1ε was identified as a novel partner of MST1. Further analysis showed that the interaction between MST1 and CK1ε was mediated by their kinase domains and enhanced by the activation of MST1. To exclude the interference of the phosphorylated YAP/TAZ, the transduction from MST1 to YAP/TAZ was blocked using anti-WW45 shRNA. In the sh-WW45 cells, MST1 still inhibited the Wnt3A-induced phosphorylation of DVL2 and Wnt/β-catenin signaling by disturbing the interaction of DVL2 and CK1ε. And the growth-suppressive effe...
Source: BJ Cell - November 4, 2013 Category: Biochemistry Authors: F Xu, Y Wang, J Chang, S Du, L Diao, N Jiang, H Wang, D Ma, J Zhang Tags: BJ Signal Source Type: research
ZNF16 (HZF1) promotes erythropoiesis and megakaryocytopoiesis via its regulation on c-KIT gene
In conclusion our data demonstrated that ZNF16 plays an important role in erythropoiesis and megakaryocytopoiesis via its regulation on c-Kit/c-Raf/MEK/ERK/c-Jun/HEY1/GATA1 cascade. (Source: BJ Cell)
Source: BJ Cell - November 1, 2013 Category: Biochemistry Authors: J Chen, X Li, R Su, L Song, F Wang, J Zhang Tags: BJ Cell Source Type: research
The cytokine-induced conformational switch of nuclear NF-{kappa}B p65 is mediated by p65 phosphorylations
The transcription factor NF-κB serves to upregulate gene expression in response to precarious signals such as the proinflammatory cytokines TNF and IL-1. Here we show that stimulation of cells with TNF or IL-1 results in a profound conformational switch of the NF-κB subunit p65, as revealed by limited proteolysis assays. We also describe the identification of a conformation-specific monoclonal antibody that preferentially immunoprecipitates the inducibly refolded p65 protein. The cytokine-triggered reconfiguration of p65 mainly occurs for p65 contained in the nuclear fraction. Phosphorylations serve as the ce...
Source: BJ Cell - October 31, 2013 Category: Biochemistry Authors: M Milanovic, M Kracht, M Lienhard Schmitz Tags: BJ Gene Source Type: research
Signal-peptide mediated translocation is regulated by a P97-AIRAPL complex
Protein homeostasis is a fundamental requirement for all living cells in order to survive in a dynamic surrounding. Proper levels of AIRAPL (Zfand2b) are required in order to maintain cellular folding capacity in metazoan, and functional impairment of AIRAPL results in acceleration of ageing and protein aggregation. However, the cellular roles of AIRAPL in this process are not known. Here we report that AIRAPL binds and forms a complex with P97 (VCP/Cdc48), Ubxd8, Npl4-Ufd1, Derlin-1 and Bag6 on the ER membrane. In spite of the fact that AIRAPL complex partners are involved in ERAD process, AIRAPL knock-down does not show ...
Source: BJ Cell - October 25, 2013 Category: Biochemistry Authors: T Glinka, J Alter, I Braunstein, L Tzach, C Wei Sheng, S Geifman, M Edelmann, B Kessler, A Stanhill Tags: BJ Cell Source Type: research
Nedd4-2 (NEDD4L) controls intracellular Na{+}-mediated activity of voltage-gated sodium channels in primary cortical neurons
Nedd4-2, a HECT-type ubiquitin-protein ligase, has been implicated in regulating several ion channels, including voltage-gated sodium (Nav) channels. In Xenopus oocytes Nedd4-2 strongly inhibits the activity of multiple Navs. However, the conditions under which Nedd4-2 mediates native Nav regulation remain uncharacterised. Using Nedd4-2 deficient mice, we demonstrate here that in foetal cortical neurons Nedd4-2 regulates Navs specifically in response to elevated intracellular Na+, but does not affect steady-state Nav activity. In dorsal root ganglia neurons from the same mice, however, Nedd4-2 does not control Nav a...
Source: BJ Cell - October 24, 2013 Category: Biochemistry Authors: J A Ekberg, N A Boase, G Y Rychkov, J Manning, P Poronnik, S Kumar Tags: BJ Cell Source Type: research
SLC22A13 catalyzes unidirectional efflux of aspartate and glutamate at the basolateral membrane of type A intercalated cells in renal collecting duct
In vertebrates, SLC22A13 is an evolutionarily conserved transport protein of the plasma membrane. In human and rat, it is principally expressed in the kidney. The precise localization and physiological function are unknown. Here, immunohistochemistry revealed that expression of SLC22A13 is confined to the basolateral membrane of type A intercalated cells in rat kidney. Double-staining confirmed that SLC22A13 co-localizes with anion exchanger 1. LC-MS difference shading showed that heterologous expression of human and rat SLC22A13 in 293 cells stimulates efflux of guanidinosuccinate, aspartate, glutamate, and taurine. Time ...
Source: BJ Cell - October 23, 2013 Category: Biochemistry Authors: C Schulz, C Fork, T Bauer, S Golz, A Geerts, E Schömig, D Gründemann Tags: BJ Metabolism Source Type: research
Ligand binding and complex formation of galectin-3 is modulated by pH variations
In conclusion, our data suggest that the formation and composition of galectin-3 networks can be fine-tuned by changes in the environmental pH. (Source: BJ Cell)
Source: BJ Cell - October 22, 2013 Category: Biochemistry Authors: T von Mach, M C. Carlsson, T Straube, U Nilsson, H Leffler, R Jacob Tags: BJ Cell Source Type: research
A novel RCE1 isoform is required for H-Ras plasma membrane localisation and is regulated by USP17
Processing of the ‘CaaX’ motif found on the carboxy termini of many proteins, including the proto-oncogene Ras, requires the ER resident protease Ras converting enzyme 1 (RCE1) and is necessary for the proper localisation and function of many of these ‘CaaX’ proteins. Here we report that several mammalian species have a novel isoform (Isoform 2) of RCE1 resulting from an alternate splice site and producing an amino terminally truncated protein. We demonstrate that both RCE1 isoform 1 and the newly identified isoform 2 are required to reinstate proper H-Ras processing and thus plasma membrane loc...
Source: BJ Cell - October 17, 2013 Category: Biochemistry Authors: J Jaworski, U Govender, C McFarlane, M de la Vega, M K. Greene, N D. Rawlings, J A. Johnston, C J. Scott, J F. Burrows Tags: BJ Signal Source Type: research
Human sorCS1 binds sortilin and hampers its cellular functions
Sortilin and sorCS1, both members of the Vps10p-D receptor family, are synthesized as precursor proteins and are converted to their mature form by enzymatic cleavage of a short N-terminal propeptide. SorCS1 does not bind its propeptide, but sortilin is able to bind not just its own propeptide but also that of sorCS1. Here we show that the propeptide region of sorCS1 contains two separate sites for binding to sortilin and that only one of these sites is removed from human (as opposed to mouse) sorCS1 during processing. This leaves mature human sorCS1 with a sortilin-binding N-terminus, which allows complex formation between...
Source: BJ Cell - October 16, 2013 Category: Biochemistry Authors: J Vejby Larsen, G Hermey, E Skipper Sørensen, T Prabakaran, E Ilsø Christensen, J Gliemann, P Madsen, C Munck Petersen Tags: BJ Cell Source Type: research
Identification of a binding element for the cytoplasmic regulator FROUNT in the membrane-proximal carboxy-terminal region of chemokine receptors CCR2 and CCR5
Chemokine receptors mediate the migration of leukocytes during inflammation. The cytoplasmic protein FROUNT binds to chemokine receptors CCR2 and CCR5, and amplifies chemotactic signals in leukocytes. Although the interaction between FROUNT and chemokine receptors is important for accurate chemotaxis, the interaction mechanism has not been elucidated. Here we identified a 16-amino-acid sequence responsible for high-affinity binding of FROUNT at the membrane-proximal carboxy (C)-terminal intracellular region of CCR2 (CCR2 Pro-C) by yeast two-hybrid analysis. Synthesized peptides corresponding to the CCR2 Pro-C sequence dire...
Source: BJ Cell - October 15, 2013 Category: Biochemistry Authors: E Toda, Y Terashima, K Esaki, S Yoshinaga, M Sugihara, Y Kofuku, I Shimada, M Suwa, S Kanegasaki, H Terasawa, K Matsushima Tags: BJ Cell Source Type: research
The regulatory mechanism of a client kinase controlling its own release from Hsp90 chaperone machinery through phosphorylation
This study is the first example showing that a client kinase directly regulates Hsp90 activity, which is a novel regulatory level for the Hsp90 chaperone machinery. We first prove that PKCγ is a client protein of Hsp90α, and that through interacting with PKCγ, Hsp90α prevents PKCγ degradation and facilitates its cytosol-to-membrane translocation and activation. Interestingly, a threonine cluster, Thr-115/425/603, of Hsp90α is specifically phosphorylated by PKCγ, and what is more interesting is this threonine cluster serves as a “phosphorylation switch” for Hsp9...
Source: BJ Cell - October 14, 2013 Category: Biochemistry Authors: X Lu, X Wang, W Zhuo, L Jia, Y Jiang, Y Fu, Y Luo Tags: BJ Cell Source Type: research
pVHL acts as a down-stream target of E2F1 to suppress E2F1 activity
The von Hippel-Lindau (VHL) gene is a well-defined tumor suppressor linked to hereditary cancer syndrome. Although it is well documented that pVHL mediates HIF-1/2α degradation under normoxia conditions, accounting for a major mechanism of pVHL in tumor suppression, it remains elusive whether other HIF-independent functions contribute to pVHL tumor suppressive function. Here, we found that pVHL is a downstream target of E2F1, which harbors E2F1 binding site in its promoter. Moreover, pVHL binds to E2F1 in vitro and in vivo, resulting in inhibition of E2F1 transcriptional activity. Mechanistic studies showed that pVH...
Source: BJ Cell - October 11, 2013 Category: Biochemistry Authors: W Ji, J Wang, W Zhang, X Liu, G Ouyang, W Xiao Tags: BJ Signal Source Type: research
Functional characterisation of the trypanosome translational repressor SCD6
The storage of translationally inactive mRNAs in cytosolic granules enables cells to react flexibly to environmental changes. In eukaryotes, Scd6/Rap55, a member of the LSm14 family, is an important factor in the formation and activity of P-bodies, where mRNA decay factors accumulate, stress granules that store mRNAs under adverse conditions, and granules that store developmentally regulated mRNAs. SCD6 from Trypanosoma brucei shares the same domain architecture as orthologous proteins in other organisms and is also present in cytosolic granules (equivalent to P-bodies). We show that TbSCD6 is a general repressor of transl...
Source: BJ Cell - October 3, 2013 Category: Biochemistry Authors: M Cristodero, B Schimanski, M Heller, I Roditi Tags: BJ Gene Source Type: research
