Search results for " Helix"
showing 10 items of 106 documents
Recruitment of HIF-1α and HIF-2α to common target genes is differentially regulated in neuroblastoma: HIF-2α promotes an aggressive phenotype
2006
In neuroblastoma specimens, HIF-2alpha but not HIF-1alpha is strongly expressed in well-vascularized areas. In vitro, HIF-2alpha protein was stabilized at 5% O2 (resembling end capillary oxygen conditions) and, in contrast to the low HIF-1alpha activity at this oxygen level, actively transcribed genes like VEGF. Under hypoxia (1% O2), HIF-1alpha was transiently stabilized and primarily mediated acute responses, whereas HIF-2alpha protein gradually accumulated and governed prolonged hypoxic gene activation. Knockdown of HIF-2alpha reduced growth of neuroblastoma tumors in athymic mice. Furthermore, high HIF-2alpha protein levels were correlated with advanced clinical stage and high VEGF expr…
Fertility and Polarized Cell Growth Depends on eIF5A for Translation of Polyproline-Rich Formins in Saccharomyces cerevisiae
2014
eIF5A is an essential and evolutionary conserved translation elongation factor, which has recently been proposed to be required for the translation of proteins with consecutive prolines. The binding of eIF5A to ribosomes occurs upon its activation by hypusination, a modification that requires spermidine, an essential factor for mammalian fertility that also promotes yeast mating. We show that in response to pheromone, hypusinated eIF5A is required for shmoo formation, localization of polarisome components, induction of cell fusion proteins, and actin assembly in yeast. We also show that eIF5A is required for the translation of Bni1, a proline-rich formin involved in polarized growth during …
Latvijas augstskolu nozīme uzņēmējdarbības ekosistēmā
2015
Augstskolas ir galvenais uzņēmējdarbības ekosistēmas attīstības virzītājspēks. Tās izglīto gan topošos darba devējus – uzņēmējus, gan arī darba ņēmējus. Tās ir viens no trim spēlētājiem Triple Helix modelī kopā ar valsti un industriju. Triple Helix modelis, ko Eckovics ir radījis 1993. gadā, izvirza priekšnosacījumus sekmīgai šo trīs modeļa dalībnieku sadarbībai, lai virzītu valsts ekonomiku pretim attīstībai. Galvenokārt visās attīstītajās valstīs šis modelis ir ieviests un būtiski uzlabo sadarbību starp industriju, augstskolām un valsti, sekmējot uzņēmējarbības attīstību. Tomēr Latvijā šis modelis nav pietiekami ņemts vērā, realizējot gan izglītības, gan arī uzņēmējdarbības vides attīstīb…
High levels of HIF-2α highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche
2007
High HIF-2alpha protein levels in the sympathetic nervous system-derived childhood tumour neuroblastoma as well as immature phenotype correlate to unfavourable outcome. Here we show that a small subset of perivascularly located, strongly HIF-2alpha-positive tumour cells (MYCN amplified) lacks expression of differentiation markers, but expresses neural crest and early sympathetic progenitor marker genes such as Notch-1, HES-1, c-Kit, dHAND, and vimentin. HIF-2alpha- and CD68-positive tumour-associated macrophages were frequently found close to the immature and HIF-2alpha-positive neuroblastoma cells and as VEGF levels are high in the perivascular niche, we hypothesize that neuroblastoma neur…
Distinct 5' SCL enhancers direct transcription to developing brain, spinal cord, and endothelium: neural expression is mediated by GATA factor bindin…
1999
The SCL gene encodes a basic helix-loop-helix transcription factor with a pivotal role in the development of endothelium and of all hematopoietic lineages. SCL is also expressed in the central nervous system, although its expression pattern has not been examined in detail and its function in neural development is unknown. In this article we present the first analysis of SCL transcriptional regulation in vivo. We have identified three spatially distinct regulatory modules, each of which was both necessary and sufficient to direct reporter gene expression in vivo to three different regions within the normal SCL expression domain, namely, developing endothelium, midbrain, and hindbrain/spinal …
Procollagen C-proteinase Enhancer Stimulates Procollagen Processing by Binding to the C-propeptide Region Only*
2011
Background: Procollagen C-proteinase enhancer-1 (PCPE-1) is an extracellular glycoprotein that increases activity of certain zinc metalloproteinases involved in tissue development and repair. Results: PCPE-1 binds uniquely to the C-propeptide region of the procollagen molecule. Conclusion: PCPE-1 enhances proteolysis by binding solely to the procollagen C-propeptides. Significance: These data may lead to future applications in the development of antifibrotic therapies.
Morphological transformations in a dually thermoresponsive coil-rod-coil bioconjugate.
2013
We report the conformational and assembly behavior of a thermoresponsive triblock biohybrid conjugate under aqueous conditions. The triblock comprises of poly(diethylene glycol methyl ether methacrylate) (PDEGMEMA) conjugated to the ends of a triple-helix forming collagen-like peptide. The circular dichroism (CD) experiment confirms the ability of the collagen-like peptide middle block to assemble as a triple helix in the hybrid conjugate. Above the LCST (∼35 °C), the collapse of the thermoresponsive PDEGMEMA polymer at the ends of the peptide domain resulted in a concomitant increase in the conformational stability of the peptide domain towards thermal denaturation. Upon cooling back, the …
Influence of the hydrophilic face on the folding ability and stability of α-helix bundles: relevance to the peptide catalytic activity
2000
Although not the sole feature responsible, the packing of amino acid side chains in the interior of proteins is known to contribute to protein conformational specificity. While a number of amphipathic peptide sequences with optimized hydrophobic domains has been designed to fold into a desired aggregation state, the contribution of the amino acids located on the hydrophilic side of such peptides to the final packing has not been investigated thoroughly. A set of self-aggregating 18-mer peptides designed previously to adopt a high level of alpha-helical conformation in benign buffer is used here to evaluate the effect of the nature of the amino acids located on the hydrophilic face on the pa…
Hypusinated eIF5A is required for the translation of collagen.
2021
ABSTRACT Translation of mRNAs that encode peptide sequences with consecutive prolines (polyproline) requires the conserved and essential elongation factor eIF5A to facilitate the formation of peptide bonds. It has been shown that, upon eIF5A depletion, yeast ribosomes stall in polyproline motifs, but also in tripeptide sequences that combine proline with glycine and charged amino acids. Mammalian collagens are enriched in putative eIF5A-dependent Pro-Gly-containing tripeptides. Here, we show that depletion of active eIF5A in mouse fibroblasts reduced collagen type I α1 chain (Col1a1) content, which concentrated around the nuclei. Moreover, it provoked the upregulation of endoplasmic reticul…
Collagen overglycosylation: a biochemical feature that may contribute to bone quality.
2005
Skeletal ability to resist mechanical stress is determined by bone amount and quality, which relies on macro- and micro-architecture, turnover, bone matrix, and mineralisation; the role of collagen has not been clearly elucidated. Numerous post-translational steps are involved in collagen type I biosynthesis, including residue hydroxylation and glycosylation catalysed by enzymes that work until the protein folds forming the triple helix; therefore, folding rate regulates these processes. Overglycosylated hydroxylysines are poor substrates for epsilon-amino group deamination which initiates cross-link formation. Three clinical conditions associated with fractures may relate collagen overglyc…