Search Results
Regulation of the tumor-suppressor function of the class III phosphatidylinositol 3-kinase complex by ubiquitin and SUMO
2014, Reidick, Christina, El Magraoui, Fouzi, Meyer, Helmut E., Stenmark, Harald, Platta, Harald W.
The occurrence of cancer is often associated with a dysfunction in one of the three central membrane-involution processes—autophagy, endocytosis or cytokinesis. Interestingly, all three pathways are controlled by the same central signaling module: the class III phosphatidylinositol 3-kinase (PI3K-III) complex and its catalytic product, the phosphorylated lipid phosphatidylinositol 3-phosphate (PtdIns3P). The activity of the catalytic subunit of the PI3K-III complex, the lipid-kinase VPS34, requires the presence of the membrane-targeting factor VPS15 as well as the adaptor protein Beclin 1. Furthermore, a growing list of regulatory proteins associates with VPS34 via Beclin 1. These accessory factors define distinct subunit compositions and thereby guide the PI3K-III complex to its different cellular and physiological roles. Here we discuss the regulation of the PI3K-III complex components by ubiquitination and SUMOylation. Especially Beclin 1 has emerged as a highly regulated protein, which can be modified with Lys11-, Lys48- or Lys63-linked polyubiquitin chains catalyzed by distinct E3 ligases from the RING-, HECT-, RBR- or Cullin-type. We also point out other cross-links of these ligases with autophagy in order to discuss how these data might be merged into a general concept.
Infrared ellipsometric study of hydrogen-bonded long-chain thiolates on gold: Towards resolving structural details
2011, Tsankov, Dimiter, Philipova, Irena, Kostova, Kalina, Hinrichs, Karsten
A set of newly synthesized aryl-substituted amides of 16-mercaptohexadecanoic acid (R = 4-OH; 3,5-di-OH) are self-assembled on Au(111) substrate. Self assembled monolayers (SAMs) formed by these molecules are studied by ellipsometry from infrared to visible spectral range. Best fit calculations based on the three-phase optical model are employed in order to determine the average tilt angle of the hydrocarbon chains. The data revealed that the SAMs reside in a crystalline-like environment as the long methylene chains predominantly exist in all-trans conformation. The calculated tilt angle of the hydrocarbon chain is decreased by approximately 12° in comparison with the one for the correspondent long-chain n-alkyl thiols. Strong hydrogen bonded networks were detected between the amide proton and the carbonyl oxygen as well as between hydroxyl groups in the end aryl substituents. The transition dipole moments of the C=O, N-H and O-H modes are oriented almost parallel to the gold surface.
Autophagy-related deubiquitinating enzymes involved in health and disease
2015, El Magraoui, Fouzi, Reidick, Christina, Meyer, Hemut E., Platta, Harald W.
Autophagy is an evolutionarily-conserved process that delivers diverse cytoplasmic components to the lysosomal compartment for either recycling or degradation. This involves the removal of protein aggregates, the turnover of organelles, as well as the elimination of intracellular pathogens. In this situation, when only specific cargoes should be targeted to the lysosome, the potential targets can be selectively marked by the attachment of ubiquitin in order to be recognized by autophagy-receptors. Ubiquitination plays a central role in this process, because it regulates early signaling events during the induction of autophagy and is also used as a degradation-tag on the potential autophagic cargo protein. Here, we review how the ubiquitin-dependent steps of autophagy are balanced or counteracted by deubiquitination events. Moreover, we highlight the functional role of the corresponding deubiquitinating enzymes and discuss how they might be involved in the occurrence of cancer, neurodegenerative diseases or infection with pathogenic bacteria.
Interaction of proteins identified in human thyroid cells
2013, Pietsch, Jessica, Riwaldt, Stefan, Bauer, Johann, Sickmann, Albert, Weber, Gerhard, Grosse, Jirka, Infanger, Manfred, Eilles, Christoph, Grimm, Daniela
Influence of gravity forces on the regulation of protein expression by healthy and malignant thyroid cells was studied with the aim to identify protein interactions. Western blot analyses of a limited number of proteins suggested a time-dependent regulation of protein expression by simulated microgravity. After applying free flow isoelectric focusing and mass spectrometry to search for differently expressed proteins by thyroid cells exposed to simulated microgravity for three days, a considerable number of candidates for gravi-sensitive proteins were detected. In order to show how proteins sensitive to microgravity could directly influence other proteins, we investigated all polypeptide chains identified with Mascot scores above 100, looking for groups of interacting proteins. Hence, UniProtKB entry numbers of all detected proteins were entered into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and processed. The program indicated that we had detected various groups of interacting proteins in each of the three cell lines studied. The major groups of interacting proteins play a role in pathways of carbohydrate and protein metabolism, regulation of cell growth and cell membrane structuring. Analyzing these groups, networks of interaction could be established which show how a punctual influence of simulated microgravity may propagate via various members of interaction chains.