SummaryBiotic and abiotic stress responses of plants are linked to developmental programs. Proteins involved in different signaling pathways are the molecular basis of this concerted interplay. In our study, we show that Arabidopsis thaliana HEAVY METAL-ASSOCIATED ISOPRENYLAT-ED PLANT PROTEIN3 (HIPP3; At5g60800) acts as an upstream regulator of stress-and development-related regulatory networks.Localization, metal-binding and stress-responsive gene expression of HIPP3 were analyzed via microscopy, protein and inductively coupled plasma (ICP)-MS analyses and quantitative real-time PCR. In addition, transcriptome and phenotype analyses of plants overexpressing HIPP3 were used to unravel its function.Our data show that HIPP3 is a nuclear, zinc-binding protein. It is repressed during drought stress and abscisic acid (ABA) treatment and, similar to other pathogen-related genes, is induced after infection with Pseudomonas syringae pv. tomato. HIPP3 overexpression affects the regulation of > 400 genes. Strikingly, most of these genes are involved in pathogen response, especially in the salicylate pathway. In addition, many genes of abiotic stress responses and seed and flower development are affected by HIPP3 overexpression. Plants overexpressing HIPP3 show delayed flowering.We conclude that HIPP3 acts via its bound zinc as an upstream regulator of the salicylatedependent pathway of pathogen response and is also involved in abiotic stress responses and seed and flower development.
Ectodomain cleavage (shedding) of transmembrane proteins by metalloproteases (MMP) generates numerous essential signaling molecules, but its regulation is not totally understood. CD44, a cleaved transmembrane glycoprotein, exerts both antiproliferative or tumor-promoting functions, but whether proteolysis is required for this is not certain. CD44-mediated contact inhibition and cellular proliferation are regulated by counteracting CD44 C-terminal interacting proteins, the tumor suppressor protein merlin (NF2) and ERM proteins (ezrin, radixin, moesin). We show here that activation or overexpression of constitutively active merlin or downregulation of ERMs inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced [as well as serum, hepatocyte growth factor (HGF), or plateletderived growth factor (PDGF)] CD44 cleavage by the metalloprotease ADAM10, whereas overexpressed ERM proteins promoted cleavage. Merlin-and ERM-modulated Ras or Rac activity was not required for this function. However, latrunculin (an actin-disrupting toxin) or an ezrin mutant which is unable to link CD44 to actin, inhibited CD44 cleavage, identifying a cytoskeletal C-terminal link as essential for induced CD44 cleavage. Cellular migration, an important tumor property, depended on CD44 and its cleavage and was inhibited by merlin. These data reveal a novel function of merlin and suggest that CD44 cleavage products play a tumor-promoting role. Neuregulin, an EGF ligand released by ADAM17 from its proform NRG1, is predominantly involved in regulating cellular differentiation. In contrast to CD44, release of neuregulin from its pro-form was not regulated by merlin or ERM proteins. Disruption of the actin cytoskeleton however, also inhibited NRG1 cleavage. This current study presents one of the first examples of substrate-selective cleavage regulation.
Since the very beginning of the Modelica development ambitions for electronic simulation exist. The electronic simulator SPICE, the SPICE models and the SPICE netlists grew to a quasi standard in electronics simulation for the last 30 years. That is why the wish arose to have SPICE models available in Modelica. This paper deals with modeling the SPICE3 models in Modelica directly extracted from the original SPICE3 source code. This courses the problem of transforming the sequential simulator-internal model descriptions of SPICE to the declarative description from Modelica. To solve this problem a way was developed and tested for some SPICE3 semiconductor models. The actual library is presented and further plans are shown.
The Modelica Standard Library was improved by adding a package of a subset of SPICE3 models which are transformed to the Modelica language. This Spice3 library contains basic models, sources, and four semiconductor devices (diode, BJT, MOSFET level 1, resistor). Extensive tests showed the correctness of model characteristics at simple circuits. Further models already prepared will be added to the Spice3 Modelica Library later on.
<p>Supplemental Material and Methods. Cell lines, Transfections, Precipitation of Proteins by TCA-DOC , Co-immunoprecipitation (Co-IP) from Cell Lysates, Preparation of Cell Lysates</p>
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