Arabidopsis Homologs of a c-Jun Coactivator Are Present Both in Monomeric Form and in the COP9 Complex, and Their Abundance Is Differentially Affected by the Pleiotropic cop/det/fus Mutations

1998 ◽  
Vol 10 (11) ◽  
pp. 1779 ◽  
Author(s):  
Shing F. Kwok ◽  
Roberto Solano ◽  
Tomohiko Tsuge ◽  
Daniel A. Chamovitz ◽  
Joseph R. Ecker ◽  
...  
Keyword(s):  
Monomeric Form

scholarly journals Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 181
Author(s):  
Francesca Zonta ◽  
Christian Borgo ◽  
Camila Paz Quezada Meza ◽  
Ionica Masgras ◽  
Andrea Rasola ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Therapeutic Strategies ◽  
The Other ◽  
Osteosarcoma Cell ◽  
Monomeric Form ◽  
New Information

CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α’) and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α’) CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α’ contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.

scholarly journals Arabidopsis Homologs of a c-Jun Coactivator Are Present Both in Monomeric Form and in the COP9 Complex, and Their Abundance Is Differentially Affected by the Pleiotropic cop/det/fus Mutations

1998 ◽  
Vol 10 (11) ◽  
pp. 1779-1790 ◽  
Author(s):  
Shing F. Kwok ◽  
Roberto Solano ◽  
Tomohiko Tsuge ◽  
Daniel A. Chamovitz ◽  
Joseph R. Ecker ◽  
...  
Keyword(s):  
Monomeric Form

GAG Multivalent Systems to interact with Langerin

2021 ◽  
Vol 28 ◽  
Author(s):  
Javier Rojo ◽  
Pedro M. Nieto ◽  
José Luis de Paz
Keyword(s):  
Extracellular Matrix ◽  
Cell Membrane ◽  
Langerhans Cells ◽  
Pivotal Role ◽  
Monomeric Form ◽  
Recognition Sites ◽  
Interaction Processes ◽  
Carbohydrate Ligands ◽  
The Way

: Langerin is a C-type Lectin expressed at the surface of Langerhans cells, which play a pivotal role in protecting organisms against pathogen infections. To address this aim, Langerin presents at least two recognition sites, one Ca2+-dependent and another one independent, capable of recognizing a variety of carbohydrate ligands. In contrast to other lectins, Langerin recognizes sulfated glycosaminoglycans (GAGs), a family of complex and heterogeneous polysaccharides present in the cell membrane and the extracellular matrix at the interphase generated in the trimeric form of Langerin but absent in the monomeric form. The complexity of these oligosaccharides has impeded the development of well-defined monodisperse structures to study these interaction processes. However, in the last few decades, an improvement of synthetic developments to achieve the preparation of carbohydrate multivalent systems mimicking the GAGs has been described. Despite all these contributions, very few examples are reported where the GAG multivalent structures are used to evaluate the interaction with Langerin. These molecules should pave the way to explore these GAG-Langerin interactions.

Erratum to “Domain Organization of the Monomeric Form of the Tom70 Mitochondrial Import Receptor” [J. Mol. Biol. 388 (2009) 1043–1058]

2009 ◽  
Vol 390 (1) ◽  
pp. 154
Author(s):  
Ryan D. Mills ◽  
Jill Trewhella ◽  
Theresa Wenli Qiu ◽  
Thomas Welte ◽  
Timothy M. Ryan ◽  
...  
Keyword(s):  
Monomeric Form ◽  
Mitochondrial Import ◽  
Domain Organization ◽  
Import Receptor

scholarly journals Subforms and In Vitro Reconstitution of the NAD-Reducing Hydrogenase of Alcaligenes eutrophus

1998 ◽  
Vol 180 (5) ◽  
pp. 1023-1029 ◽  
Author(s):  
Christian Massanz ◽  
Silke Schmidt ◽  
Bärbel Friedrich
Keyword(s):  
Alcaligenes Eutrophus ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Monomeric Form ◽  
Structural Genes ◽  
Wild Type ◽  
Catalytic Function ◽  
C Terminus ◽  
In Vitro Reconstitution ◽  
Reducing Activity

The cytoplasmic, NAD-reducing hydrogenase (SH) of Alcaligenes eutrophus H16 is a heterotetrameric enzyme which contains several cofactors and undergoes a complex maturation during biogenesis. HoxH is the Ni-carrying subunit, and together with HoxY it forms the hydrogenase dimer. HoxF and HoxU represent the flavin-containing diaphorase moiety, which is closely related to NADH:ubiquinone oxidoreductase and mediates NADH oxidation. A variety of mutations were introduced into the four SH structural genes to obtain mutant enzymes composed of monomeric and dimeric forms. A deletion removing most ofhoxF, hoxU, and hoxY led to the expression of a HoxH monomer derivative which was proteolytically processed at the C terminus like the wild-type polypeptide. While the hydrogenase dimer, produced by a strain deleted of hoxF andhoxU, displayed H2-dependent dye-reducing activity, the monomeric form did not mediate the activation of H2, although nickel was incorporated into HoxH. Deletion ofhoxH and hoxY led to the production of HoxFU dimers which displayed NADH:oxidoreductase activity. Mixing the hydrogenase and the diaphorase moieties in vitro reconstituted the structure and catalytic function of the SH holoenzyme.

scholarly journals Perphenazine-macrocycle conjugates divert Aβ42 towards non-toxic aggregates by monomer sequestration

2020 ◽  
Author(s):  
Sarah R Ball ◽  
Julius S P Adamson ◽  
Michael A Sullivan ◽  
Manuela R Zimmermann ◽  
Victor Lo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nmr Spectroscopy ◽  
Kinetic Analysis ◽  
Amyloid Β ◽  
Dimensional Structure ◽  
Amyloid Β Peptide ◽  
Monomeric Form ◽  
Starting Point ◽  
The Impact

AbstractThe amyloid-β peptide, the main protein component of amyloid plaques in Alzheimer’s disease, plays a key role in the neurotoxicity associated with the condition through the formation of small toxic oligomer species which mediate the disruption of calcium and glutamate homeostasis. The lack of therapeutic benefit associated with removal of mature amyloid-β fibrils has focused attention on the toxic oligomeric species formed during the process of fibril assembly. Here, we present the design and synthesis of a family of perphenazine-macrocyle conjugates. We find that two-armed perphenazine-cyclam conjugates divert the monomeric form of the amyloid-β peptide away from the amyloidogenic pathway into amorphous aggregates that are not toxic to differentiated SH-SY5Y cells in vitro. This strategy prevents the formation of damaging amyloid oligomers. Kinetic analysis of the effects of these compounds on the assembly pathway, together with NMR spectroscopy, identifies rapid monomer sequestration as the underlying neuroprotective mechanism. The ability to specifically target the monomeric form of amyloid-β allows for further understanding of the impact of the multiple species formed between peptide biogenesis and plaque deposition. The modular, three-dimensional structure of these compounds provides a starting point for the design of more potent modulators of this amyloid-forming peptide, and can be adapted to probe the protein self-assembly pathways associated with other proteinopathies.Significance statementThe aggregation pathway of the amyloid-β (Aβ) peptide in Alzheimer’s disease is complex and involves multiple different species. An inability to isolate and study the impact of distinct Aβ species has undermined efforts to develop effective therapies. To address this issue, we have developed a series of molecules that specifically sequester the monomeric form of the highly aggregation-prone Aβ42 peptide. Interaction with these molecules diverts Aβ42 from the amyloidogenic pathway and prevents formation of toxic oligomeric species. We use kinetic analysis and NMR spectroscopy to identify rapid monomer sequestration as the underlying neuroprotective mechanism. Future rational development of these molecules and characterisation of their interactions with Aβ will delineate the impact of different Aβ oligomers on neurobiology and pathology.

Phosphinohydrazines. Part IV. Coordination compounds of N,N-dimethyl,N′-diphenylphosphinohydrazine and N,N-dimethyl-N′-diphenylthiophosphinatohydrazine

1970 ◽  
Vol 48 (3) ◽  
pp. 401-404 ◽  
Author(s):  
E. W. Ainscough ◽  
L. K. Peterson ◽  
D. E. Sabourin
Keyword(s):  
Molecular Weight ◽  
Nuclear Magnetic Resonance ◽  
Coordination Compounds ◽  
Donor Site ◽  
Membered Ring ◽  
Monomeric Form ◽  
Coordinate Structure ◽  
Polar Solvents ◽  
Uncertain Structure ◽  
Ring Structures

A study of complexes of (a) N,N-dimethyl,N′-diphenylphosphinohydrazine, DPH, viz., Pd(DPH)Cl2, Pd(DPH)2Cl2, [Pd(DPH)2Cl]ClO4, Pt(DPH)2Cl2, Pt(DPH)Cl4, Hg(DPH)Cl2; (b) N,N-dimethyl,N´-diphenylthiophosphinatohydrazine, DPS, viz., Pd(DPS)Cl2, Pt(DPS)Cl4, Ag(DPS)NO3, Zn(DPS)Cl2, Cd(DPS)Cl2, and Hg(DPS)Cl2, and (c) N,N-dimethylhydrazine, DMH, viz., Zn(DMH)2Cl2 and Cd(DMH)Cl2, has been carried out using conductivity, molecular weight, infrared, and nuclear magnetic resonance measurements. DPH functions mostly as a unidentate ligand, with the phosphorus atom as the preferred donor site. Thus Pd(DPH)Cl2 is a chlorobridged dimer in solution in weakly polar solvents, while the monomeric form in polar solvents is of uncertain structure. A trans, four-coordinate structure is consistent for Pd(DPH)2Cl2. For [Pd(DPH)2Cl]ClO4, however, one DPH ligand is chelating through the phosphorus and terminal nitrogen atoms, while the second ligand is unidentate; the compound is a monomeric uni–univalent electrolyte in nitrobenzene. The ligand DPS appears to chelate via the sulfur and central nitrogen atoms, giving four-membered ring structures; a cis configuration is suggested for Pd(DPS)Cl2. Zn(DMH)2Cl2 is monomeric in solution, with the Me2N group coordinated to the metal.

scholarly journals High mobility group proteins of amphibian oocytes: a large storage pool of a soluble high mobility group-1-like protein and involvement in transcriptional events.

1983 ◽  
Vol 97 (3) ◽  
pp. 838-848 ◽  
Author(s):  
J A Kleinschmidt ◽  
U Scheer ◽  
M C Dabauvalle ◽  
M Bustin ◽  
W W Franke
Keyword(s):  
Rana Temporaria ◽  
Peptide Mapping ◽  
Gradient Centrifugation ◽  
High Mobility ◽  
High Mobility Group ◽  
Monomeric Form ◽  
Hmg Proteins ◽  
Amphibian Species ◽  
Large Oocyte ◽  
Calf Thymus

Oocytes of several amphibian species (Xenopus laevis, Rana temporaria, and Pleurodeles waltlii) contained a relatively large pool of nonchromatin-bound, soluble high mobility group (HMG) protein with properties similar to those of calf thymus proteins HMG-1 and HMG-2 (protein HMG-A; A, amphibian). About half of this soluble HMG-A was located in the nuclear sap, the other half was recovered in enucleated ooplasms. This protein was identified by its mobility on one- and two-dimensional gel electrophoresis, by binding of antibodies to calf thymus HMG-1 to polypeptides electrophoretically separated and blotted on nitrocellulose paper, and by tryptic peptide mapping of radioiodinated polypeptides. Most, if not all, of the HMG-A in the soluble nuclear protein fraction, preparatively defined as supernatant obtained after centrifugation at 100,000 g for 1 h, was in free monomeric form, apparently not bound to other proteins. On gel filtration it eluted with a mean peak corresponding to an apparent molecular weight of approximately 25,000; on sucrose gradient centrifugation it appeared with a very low S value (2-3 S), and on isoelectric focusing it appeared in fractions ranging from pH approximately 7 to 9. This soluble HMG-A was retained on DEAE-Sephacel but could be eluted already at moderate salt concentrations (0.2 M KCl). In oocytes of various stages of oogenesis HMG-A was accumulated in the nucleus up to concentrations of approximately 14 ng per nucleus (in Xenopus), corresponding to approximately 0.2 mg/ml, similar to those of the nucleosomal core histones. This nuclear concentration is also demonstrated using immunofluorescence microscopy. When antibodies to bovine HMG-1 were microinjected into nuclei of living oocytes of Pleurodeles the lateral loops of the lampbrush chromosomes gradually retracted and the whole chromosomes condensed. As shown using electron microscopy of spread chromatin from such injected oocyte nuclei, this process of loop retraction was accompanied by the appearance of variously-sized and irregularly-spaced gaps within transcriptional units of chromosomal loops but not of nucleoli, indicating that the transcription of non-nucleolar genes was specifically inhibited by this treatment and hence involved an HMG-1-like protein. These data show that proteins of the HMG-1 and -2 category, which are usually chromatin-bound components, can exist, at least in amphibian oocytes, in a free soluble monomeric form, apparently not bound to other molecules. The possible role of this large oocyte pool of soluble HMG-A in early embryogenesis is discussed as well as the possible existence of soluble HMG proteins in other cells.

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