Search results for "binding proteins"
showing 10 items of 911 documents
The “Janus” Role of C/EBPs Family Members in Cancer Progression
2020
CCAAT/enhancer-binding proteins (C/EBPs) constitute a family of transcription factors composed of six members that are critical for normal cellular differentiation in a variety of tissues. They promote the expression of genes through interaction with their promoters. Moreover, they have a key role in regulating cellular proliferation through interaction with cell cycle proteins. C/EBPs are considered to be tumor suppressor factors due to their ability to arrest cell growth (contributing to the terminal differentiation of several cell types) and for their role in cellular response to DNA damage, nutrient deprivation, hypoxia, and genotoxic agents. However, C/EBPs can elicit completely opposi…
Lipid chaperones and associated diseases: a group of chaperonopathies defining a new nosological entity with implications for medical research and pr…
2020
AbstractFatty acid–binding proteins (FABPs) are lipid chaperones assisting in the trafficking of long-chain fatty acids with functions in various cell compartments, including oxidation, signaling, gene-transcription regulation, and storage. The various known FABP isoforms display distinctive tissue distribution, but some are active in more than one tissue. Quantitative and/or qualitative changes of FABPs are associated with pathological conditions. Increased circulating levels of FABPs are biomarkers of disorders such as obesity, insulin resistance, cardiovascular disease, and cancer. Deregulated expression and malfunction of FABPs can result from genetic alterations or posttranslational mo…
The b1 isoform of protocadherin-gamma (Pcdhgamma) interacts with the microtubule-destabilizing protein SCG10.
2004
Due to their structural characteristics and their diversity, the 22 members of the protocadherin-gamma (Pcdhgamma) family have been suggested to contribute to the establishment of specific connections in the nervous system. Here, we focus on a single isoform, Pcdhgamma-b1. Its expression is found in different brain regions and in developing spinal cord it is restricted to scattered cells, whereas all cells are labeled using an antibody that recognizes all Pcdhgamma isoforms. As a first step to understanding the signaling mechanisms downstream of Pcdhgamma, we identify the microtubule-destabilizing protein SCG10 as a cytoplasmic interactor for Pcdhgamma-b1 and other isoforms of the Pcdhgamma…
Centrins, gatekeepers for the light-dependent translocation of transducin through the photoreceptor cell connecting cilium
2006
Centrins are members of a highly conserved subgroup of the EF-hand superfamily of Ca(2+)-binding proteins commonly associated with centrosome-related structures. In the retina, centrins are also prominent components of the photoreceptor cell ciliary apparatus. Centrin isoforms are differentially localized at the basal body and in the lumen of the connecting cilium. All molecular exchanges between the inner and outer segments occur through this narrow connecting cilium. Ca(2+)-activated centrin isoforms bind to the visual heterotrimeric G-protein transducin via an interaction with the betagamma-subunit. Ca(2+)-dependent assemblies of centrin/G-protein complexes may regulate the transducin mo…
Alternative Polyadenylation Events Contribute to the Induction of NF-ATc in Effector T Cells
1999
Abstract The transcription factor NF-ATc is synthesized in three prominent isoforms. These differ in the length of their C terminal peptides and mode of synthesis. Due to a switch from the use of a 3′ polyA site to a more proximal polyA site, NF-ATc expression switches from the synthesis of the two longer isoforms in naive T cells to that of short isoform A in T effector cells. The relative low binding affinity of cleavage stimulation factor CstF-64 to the proximal polyA site seems to contribute to its neglect in naive T cells. These alternative polyadenylation events ensure the rapid accumulation of high concentrations of NF-ATc necessary to exceed critical threshold levels of NF-ATc for g…
Regulation of the expression of inducible nitric oxide synthase
2010
Nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase (iNOS) is involved in complex immunomodulatory and antitumoral mechanisms and has been described to have multiple beneficial microbicidal, antiviral and antiparasital effects. However, dysfunctional induction of iNOS expression seems to be involved in the pathophysiology of several human diseases. Therefore iNOS has to be regulated very tightly. Modulation of expression, on both the transcriptional and post-transcriptional level, is the major regulation mechanism for iNOS. Pathways resulting in the induction of iNOS expression vary in different cells or species. Activation of the transcription factors NF-kappaB an…
Selective Activation of Trophoblast-specific PLAC1 in Breast Cancer by CCAAT/Enhancer-binding Protein β (C/EBPβ) Isoform 2
2009
The trophoblast-specific gene PLAC1 (placenta-specific 1) is ectopically expressed in a wide range of human malignancies, most frequently in breast cancer, and is essentially involved in cancer cell proliferation, migration, and invasion. Here we show that basal activity of the PLAC1 promoter is selectively controlled by ubiquitous transcription factor SP1 and isoform 2 of CCAAT/enhancer-binding protein beta that we found to be selectively expressed in placental tissue and cancer cells. Binding of both factors to their respective elements within the PLAC1 promoter was essential to attain full promoter activity. Estrogen receptor alpha (ERalpha) signaling further augmented transcription and …
Autoregulation of NFATc1/A Expression Facilitates Effector T Cells to Escape from Rapid Apoptosis
2002
AbstractThreshold levels of individual NFAT factors appear to be critical for apoptosis induction in effector T cells. In these cells, the short isoform A of NFATc1 is induced to high levels due to the autoregulation of the NFATc1 promoter P1 by NFATs. P1 is located within a CpG island in front of exon 1, represents a DNase I hypersensitive chromatin site, and harbors several sites for binding of inducible transcription factors, including a tandemly arranged NFAT site. A second promoter, P2, before exon 2, is not controlled by NFATs and directs synthesis of the longer NFATc1/B+C isoforms. Contrary to other NFATs, NFATc1/A is unable to promote apoptosis, suggesting that NFATc1/A enhances eff…
Centrins in retinal photoreceptor cells: regulators in the connecting cilium.
2008
Changes in the intracellular Ca2+ concentration regulate the visual signal transduction cascade directly or more often indirectly through Ca2+-binding proteins. Here we focus on centrins, which are members of a highly conserved subgroup of the EF-hand superfamily of Ca2+-binding proteins in photoreceptor cells of the vertebrate retina. Centrins are commonly associated with centrosome-related structures. In mammalian retinal photoreceptor cells, four centrin isoforms are expressed as prominent components in the connecting cilium linking the light-sensitive outer segment compartment with the metabolically active inner segment compartment. Our data indicate that Ca2+-activated centrin isoforms…
ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated…
2022
Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived mi…