Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted a functional analysis of the promoter for the human ferritin heavy chain-encoding gene (pFERH) in HepG2 and HeLa cells. The activity of pFERH is equivalent in both cell types, despite their different ferritin (Fer) isotypes. Transfections of a series of 5'-deletion mutants indicate that pFERH activity is essentially dependent on two motifs. One of them, accounting for about 50% of the total transcriptional activity, is recognized by the RNA polymerase II transcription factor, Sp1, and the other by a low-affinity factor present in both the cell types analyzed.
 ...
PMID:Promoter for the human ferritin heavy chain-encoding gene (FERH): structural and functional characterization. 154 3

This review has considered what is known about the precise chemical mechanisms involved in the signal transduction of heavy metal ions. By reviewing what is known about general modes of signal transduction, we may draw parallels with the detection of and response to metal ions. In all forms of signal transduction, sensors and transducers are required. Yet, it is apparent that each system has unique features which undoubtedly are critical for the specific signal at hand. Within the context of metal-responsive systems, regardless of whether or not the metal ion is being sequestered, directly utilized, removed or otherwise, several examples of specific metalloregulatory proteins have been elucidated and are summarized in Table II. A close inspection of Table II reveals that in most signal transduction pathways for heavy metals, the presence of the metal ion causes a marked change in the nucleic acid binding capacity of the metalloregulatory protein. For example, the presence of iron results in the dissociation of a protein from iron responsive elements, thereby derepressing ferritin translation. In other instances, metal binding allows a metalloregulatory protein to associate with DNA to activate or repress transcription, as with ACE1 and Fur, respectively. In fact, to the authors' knowledge, it appears that all characterized ligand-responsive transcription factors change nucleic acid binding activity upon ligand binding. This change in affinity is a major feature of the mechanism for activation or repression by these receptors. In contrast, the mercuric ion metalloregulatory protein, MerR, operates by an entirely different transduction mechanism. MerR remains bound to its operator sequence in the presence and absence of mercuric ion, with only a slight increase in the dissociation rate constant in the presence of Hg(II). Furthermore, the site of MerR binding to the DNA is in a novel position for a prokaryotic activator, directly between the two sets of recognition sequences for RNA polymerase. Analysis of the protein-DNA interactions and transcriptional activity has demonstrated that MerR forms a complex with RNA polymerase in the absence of Hg(II) that is unstable and transcriptionally repressed. When Hg(II) is present in greater than nanomolar concentrations, a highly active transcription complex is formed at PT and a distortion at the center of the palindromic MerR binding site is detectable. Kinetic analysis has determined that, although no change in the binding of RNAP to PT is apparent, the presence of Hg(II) stimulates the rate of isomerization from the closed to the open transcription complex.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Metalloregulatory proteins and molecular mechanisms of heavy metal signal transduction. 220 24

Incubation of HeLa cells for 24 h with either hydroxyurea (HU), aphidicolin (APHI), thymidine (T) or butyrate (BU), substances used to inhibit replication and accumulate cells at the G1/S interphase, followed by the elimination of the inhibitor and the addition of iron to the growth medium, results in an immediate (HU, APHI, T) or slightly delayed (BU) increased accumulation (18-24-fold higher than the basal level) of ferritin. Under the same experimental circumstances, 5-azacytidine is without effect. As a result of the action of these inhibitors on the structure of DNA, it is proposed that ferritin genes remain accessible to RNA polymerase allowing the accumulation in the cytoplasm of mature ferritin mRNA ready to be mobilized by iron for the production of ferritin molecules.
 ...
PMID:Stimulation of protein accumulation in HeLa cells by inhibitors of DNA replication. Ferritin. 241 93

The localization of foot-and-mouth disease viral-induced RNA polymerase has been determined in situ and in partially fractionated cell components by using polymerase antisera tagged with either peroxidase or ferritin. Electron microscopic examination revealed the polymerase to be heavily concentrated on membranes of the smooth membranous vacuoles (SMV) which are newly formed during infection and which were previously shown to be the site where newly synthesized viral RNA appeared. Polymerase antigen was also seen to be associated with the endoplasmic reticulum (ER), the assumed site of original synthesis, and to a lesser extent with mitochondria and the Golgi apparatus. There was no significant polymerase attachment to nuclear and plasma membranes.
 ...
PMID:Association of foot-and-mouth disease virus induced RNA polymerase with host cell organelles. 631 90

We have cloned cDNA copies of the immunoglobulin heavy and light chain genes from hybridoma cells able to produce antibody against human ferritin. Variable segments of these genes were obtained using the polymerase chain reaction (PCR). The specific amplifications of ligase reaction products were carried out to combine the variable segments with DNA fragments coding for a peptide-linker and for a signal peptide of the cloned pelB gene of Erwinia carotovora. During the antiferritin single-chain antibody gene expression under the T7 RNA polymerase control in E. coli the processed molecules of recombinant proteins formed aggregates in periplasm. The reversible denaturation in the absence of reducing agents had allowed us to obtain single-chain antibodies with the original binding specificity toward human ferritin.
 ...
PMID:[Preparation of single-chained antibodies to human ferritin in Escherichia coli]. 848 73

The ferritin gene (cft) of Campylobacter jejuni was overexpressed in cells of Escherichia coli using a T7 RNA polymerase expression system. Many round particles which were the same size as the ferritin particles purified from C. jejuni were observed in the lysate of the cft-overexpressed E. coli cells. Since most of them were devoid of a central electron dense core consisting of ferric irons, the Campylobacter ferritins over-produced in E. coli seemed to be apoferritin. When large amounts of ferrous iron (supplied as FeSO4) were added to culture medium, the cft-overexpressed cells formed large inclusion bodies of paracrystalline arrays comprised of ferritin particles with central electron dense cores. The addition of ferric irons did not produce paracrystalline inclusion.
 ...
PMID:Overproduction of Campylobacter ferritin in Escherichia coli and induction of paracrystalline inclusion by ferrous compound. 925 Oct 57

The transcription of the human H ferritin gene is regulated by a transcription factor, called Bbf, which binds an enhancer element located in the -100/+1 region of the H promoter. To evaluate a possible role of Bbf phosphorylation on the promoter efficiency, we exposed HeLa cells to the phosphatase inhibitor okadaic acid (OA). The okadaic acid treatment increased about 4-fold the transcription driven by the -100/+1 region of the H promoter. However, the DNA binding activity of Bbf was not modified by OA, as assessed by EMSA. Immunoprecipitation experiments demonstrated that the OA-treatment stimulates and/or stabilizes the complex between Bbf and the nuclear protein p300, most probably by inducing the phosphorylation state of the complex. Bbf depends on the p300 molecule to trigger RNA polymerase II and thus transcription of the H ferritin gene.
 ...
PMID:Okadaic acid stimulates H ferritin transcription in HeLa cells by increasing the interaction between the p300 CO-activator molecule and the transcription factor Bbf. 936 6

We analysed the role of the nuclear protein P/CAF in regulating the transcription of the gene for human heavy (H) ferritin in given cell types. P/CAF is a histone acetylase, recruited to specific promoters via interaction with the co-activator molecule p300/CREB-binding protein (CBP). Histone acetylation promoted by P/CAF destabilizes the nucleosome structure, thus contributing to activation of transcription. The transcription of the H ferritin gene is regulated by the transcription factor B-box-binding factor (Bbf), which bridges RNA polymerase II via p300/CBP. Northern blot analyses of RNA species from various human tissues and cell lines demonstrate that the H ferritin gene is expressed at high levels in cells containing high levels of the P/CAF transcript. Moreover, transient overexpression of P/CAF in cells constitutively expressing low levels of this protein activates transcription driven by the region of the H promoter interacting with Bbf. The involvement of p300/CBP in the possible P/CAF-mediated regulation of H promoter was also explored by evaluating the phenomenon in the presence of the oncoprotein E1A. The results of these experiments demonstrate that P/CAF activates the H promoter also in the presence of limited amounts of p300/CBP. We argue that P/CAF is a component of the basal transcription apparatus of the H ferritin gene and that the relative amounts of the P/CAF protein in different cell types could account for the cell-specific control of the H ferritin gene transcription.
 ...
PMID:P/CAF/p300 complex binds the promoter for the heavy subunit of ferritin and contributes to its tissue-specific expression. 979 90

We are interested in learning how iron is safely inserted and stored in ferritin. Recombinant DNA technology has considerable potential in determining the functional roles of the two ferritin subunits (H and L). In previous studies, we have observed that recombinant rat H ferritin was repressive to cell growth in both prokaryotic and eukaryotic expression systems (Guo et al., Biochem. Biophys. Res. Commun. 242, 39-45 (1998)). This results in the protein being expressed at very low levels. This problem was partially bypassed by the use of an inducible expression system, which utilizes T7 RNA polymerase dependent expression of the gene, induced by isopropyl beta-D-thiogalactopyranoside (IPTG). Simultaneously expressing the H and L ferritin genes in this system resulted in only a narrow range of ferritin heteromers, which predominantly consisted of the L subunit. Addition of rifampicin to cultures, 1 h following the induction of protein synthesis by IPTG, increased the production of the H subunit and thus increased the range of ferritin H:L subunit ratios. Simultaneous expression of the H and L ferritin genes in Escherichia coli grown in a deficient medium with minimal iron and with the addition of rifampicin resulted in the production of a range of recombinant human apoferritin heteromers that could be separated based on their subunit composition.
 ...
PMID:Production of recombinant human apoferritin heteromers. 1114 22

Alport disease is caused by mutations in genes encoding the alpha3, alpha4, or alpha5 chains of type IV collagen, which form the collagenous network of mature glomerular basement membrane (GBM). In the absence of alpha3, alpha4, alpha5 (IV) collagen, alpha1, alpha2 (IV) collagen persists, which ordinarily is found only in GBM of developing kidney. In addition to dysregulation of collagen IV, Alport GBM contains aberrant laminins, which may contribute to the progressive GBM thickening and splitting, proteinuria, and renal failure seen in this disorder. This study sought to characterize further the laminin dysregulation in collagen alpha3(IV) knockout mice, a model of Alport disease. With the use of confocal microscopy, laminin alpha1 and alpha5 abundance was quantified, and it was found that they co-distributed in significantly large amounts in areas of GBM thickening. In addition, labeling of entire glomeruli for laminin alpha5 was significantly greater in Alport mice than in wild-type siblings. Reverse transcriptase-PCR from isolated glomeruli demonstrated significantly more laminin alpha5 mRNA in Alport mice than in wild-type controls, indicating upregulated transcription of Lama5. For testing glomerular barrier function, ferritin was injected into 2-wk-old Alport and control mice, and GBM was examined by electron microscopy. Highest ferritin levels were seen in Alport GBM thickenings beneath effaced podocyte foot processes, but morphologically normal GBM was significantly permeable as well. We concluded that (1) ultrastructurally normal Alport GBM residing beneath differentiated podocyte foot processes is inherently and abnormally permeable, and (2) upregulation of Lama5 transcription and concentration of laminin alpha1 and alpha5 within Alport GBM thickenings contribute to abnormal permeabilities.
 ...
PMID:Laminin compensation in collagen alpha3(IV) knockout (Alport) glomeruli contributes to permeability defects. 1769 9


1 2 Next >>