Search results for "script"
showing 10 items of 5143 documents
Cell cycle independent role of Cyclin E during neural cell fate specification in Drosophila is mediated by its regulation of Prospero function
2009
AbstractDuring development, neural progenitor cells or neuroblasts generate a great intra- and inter-segmental diversity of neuronal and glial cell types in the nervous system. In thoracic segments of the embryonic central nervous system of Drosophila, the neuroblast NB6-4t undergoes an asymmetric first division to generate a neuronal and a glial sublineage, while abdominal NB6-4a divides once symmetrically to generate only 2 glial cells. We had earlier reported a critical function for the G1 cyclin, CyclinE (CycE) in regulating asymmetric cell division in NB6-4t. Here we show that (i) this function of CycE is independent of its role in cell cycle regulation and (ii) the two functions are m…
Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1
2001
Glucocorticoids inhibit the proinflammatory activities of transcription factors such as AP-1 and NF-kappa B as well as that of diverse cellular signaling molecules. One of these signaling molecules is the extracellular signal-regulated kinase (Erk-1/2) that controls the release of allergic mediators and the induction of proinflammatory cytokine gene expression in mast cells. The mechanism of inhibition of Erk-1/2 activity by glucocorticoids is unknown. Here we report a novel dual action of glucocorticoids for this inhibition. Glucocorticoids increase the expression of the MAP kinase phosphatase-1 (MKP-1) gene at the promoter level, and attenuate proteasomal degradation of MKP-1, which we re…
The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin
2021
Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a growing number of reports on their function in protein interactions regulated by post-translational modifications. LCRs facilitate the increase of regulatory and network complexity required with the emergence of organisms with more complex tissue distribution and development. Although the low conservation and structural flexibility of LCRs complicate their study, evolutionary studies of proteins …
Co-regulator recruitment and the mechanism of retinoic acid receptor synergy.
2002
Crystal structure and co-regulator interaction studies have led to a general mechanistic view of the initial steps of nuclear receptor (NR) action. Agonist-induced transconformation of the ligand-binding domain (holo-LBD) leads to the formation of co-activator complexes, and destabilizes the co-repressor complexes bound to the ligand-free (apo) LBD. However, the molecular basis of retinoid-X receptor (RXR) 'subordination' in heterodimers, an essential mechanism to avoid signalling pathway promiscuity, has remained elusive. RXR, in contrast to its heterodimer partner, cannot autonomously induce transcription on binding of cognate agonists. Here we show that RXR can bind ligand and recruit co…
Investigation of protein folding by coarse-grained molecular dynamics with the UNRES force field.
2010
Coarse-grained molecular dynamics simulations offer a dramatic extension of the time-scale of simulations compared to all-atom approaches. In this article, we describe the use of the physics-based united-residue (UNRES) force field, developed in our laboratory, in protein-structure simulations. We demonstrate that this force field offers about a 4000-times extension of the simulation time scale; this feature arises both from averaging out the fast-moving degrees of freedom and reduction of the cost of energy and force calculations compared to all-atom approaches with explicit solvent. With massively parallel computers, microsecond folding simulation times of proteins containing about 1000 r…
Different protein turnover of interleukin-6-type cytokine signalling components.
1999
Interleukin (IL)-6 and IL-6-type cytokines signal through the gp130/Jak/STAT signal transduction pathway. The key components involved are the signal transducing receptor subunit gp130, the Janus kinases Jak1, Jak2 and Tyk2, STAT1 and STAT3 of the family of signal transducers and activators of transcription, the protein tyrosine phosphatase SHP2 and the suppressors of cytokine signalling SOCS1, SOCS2 and SOCS3. Whereas considerable information has been accumulated concerning the time-course of activation for the individual signalling molecules, data on the availability of the proteins involved in IL-6-type cytokine signal transduction are scarce. Nevertheless, availability of these molecules…
Might exogenous circular RNAs act as protein-coding transcripts in plants?
2021
Circular RNAs (circRNAs) are regulatory molecules involved in the modulation of gene expression. Although originally assumed as non-coding RNAs, recent studies have evidenced that animal circRNAs can act as translatable transcripts. The study of plant-circRNAs is incipient, and no autonomous coding plant-circRNA has been described yet. Viroids are the smallest plant-pathogenic circRNAs known to date. Since their discovery 50 years ago, viroids have been considered valuable systems for the study of the structure-function relationships in RNA, essentially because they have not been shown to have coding capacity. We used two pathogenic circRNAs (Hop stunt viroid and Eggplant latent viroid) as …
Identification of new claudin family members by a novel PSI-BLAST based approach with enhanced specificity.
2006
In an attempt to develop a novel strategy for the identification of new members of protein families by in silico approaches, we have developed a semi-automated procedure of consecutive PSI-BLAST (Position-Specific-Iterated Basic Local Alignment Search Tool) searches incorporating identificiation as well as subsequent validation of putative candidates. For a proof of concept study we chose the search for novel members of the claudin family. The initial step was an iterated PSI-BLAST search starting with the PMP22_Claudin domain of each known member of the claudin family against the human part of the RefSeq Database. Putative new claudin domains derived from the converged list were evaluated …
Proteins participating to the post-transcriptional regulation of the mitochondrial cytochrome c oxidase subunit IV via elements located in the 3′UTR
2009
Abstract In developing rat brain cytochrome c oxidase subunit IV (COXIV) expression is also regulated at post-transcriptional level and two 3′UTR-COXIV RNA-binding factors have been identified. Here, we report the enrichment and identification of the factors from just born rat brains by affinity chromatography of biotinylated 3′UTR-COXIV RNA–protein complexes on streptavidin-conjugated paramagnetic particles. We successfully isolated two main proteins of about 86 and 42 kDa, whose sequences were highly attributable to Hsp90 and Actin. The purified proteins maintain RNA-binding ability and specificity for COXIV messenger and, interacting with the 3′UTR, then could negatively modulate mRNA tr…
Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity
2009
Heat shock protein 27 (HSP27) accumulates in stressed cells and helps them to survive adverse conditions. We have already shown that HSP27 has a function in the ubiquitination process that is modulated by its oligomerization/phosphorylation status. Here, we show that HSP27 is also involved in protein sumoylation, a ubiquitination-related process. HSP27 increases the number of cell proteins modified by small ubiquitin-like modifier (SUMO)-2/3 but this effect shows some selectivity as it neither affects all proteins nor concerns SUMO-1. Moreover, no such alteration in SUMO-2/3 conjugation is achievable by another HSP, such as HSP70. Heat shock factor 1 (HSF1), a transcription factor responsib…