Disease relevance of BFSP1

• This effect was mimicked by exposing cells to 2 structurally unrelated iron-chelating agents, desferrioxamine (DFO) and hydroxypyridines (CP-94), and it appeared specific for hypoxia in that no modulation of apoptosis was observed with mitochondrial electron transport inhibitors, glucose deprivation, or heat shock [1].
• DFO and CP94 (1,2,diethyl-HPO) at the same dose also caused lymphopenia but marrow cellularity was unaffected [2].
• The iron chelating hydroxypyridinone, CP94, has been administered prophylactically to iron overloaded gerbils in a dosing regime which favors the formation of bidentate chelated iron, to examine the possibility of additional toxicity being caused to the liver and heart by the bidentate chelated iron complex [3].
• Potentiation of iron accumulation in cardiac myocytes during the treatment of iron overload in gerbils with the hydroxypyridinone iron chelator CP94 [3].

High impact information on BFSP1

• The recent publication of the sequences for two major lens filament proteins (CP49 and filensin) and the reconstitution in vitro of structures closely resembling beaded filaments, suggests that the beaded filament is related structurally to intermediate filaments (IFs) [4].
• BFs consist of filensin and phakinin, two recently characterized intermediate filament (IF) proteins [5].
• Filensin and phakinin copolymerize and form filamentous structures when expressed transiently in cultured cells [5].
• Quantitative immunoblotting with whole lens fiber cell preparations and fractions of washed lens membranes suggest that the natural stoichiometry of phakinin to filensin is approximately 3:1 [6].
• Radiolabeled filensin binds specifically to lens vimentin under isotonic conditions, as demonstrated by affinity chromatography and ligand-blotting assays [7].

Biological context of BFSP1

• From our results, we conclude that the gene for human CP 115 resides on chromosome 20 and the gene for human CP 47 on chromosome 3 [8].
• Amplification of CP 115 or CP 47 sequences in each of the somatic cell hybrid samples was correlated with the presence/absence of human genomic DNA sequences encoding the respective gene sequences [8].
• RESULTS: The proteomics approach used to identify affinity-purified proteins revealed the lens-specific intermediate filament proteins filensin and CP49 [9].
• Coincidently, the beaded filament polymer and the proteins filensin and CP49 are specific to lens fibre cells and are therefore excellent markers for fibre cell differentiation [10].
• These cells run into cellular senescence due to shortening of the telomeres and also commit differentiation as indicated by the accumulation of the differentiation markers, beta-crystallin and filensin. hTERT prevents the occurrence of both events [11].

Anatomical context of BFSP1

• We have studied the molecular properties of a 100-kD protein, termed filensin, which we have isolated from porcine lens membranes [7].
• The cells of the eye lens contain the type III intermediate filament protein vimentin, as well as two other intermediate filament proteins, CP49 and filensin [12].
• It is proposed that both filensin and CP49 are critically involved in organising the cytoplasmic and plasma membrane domains of the fibre cell and therefore essential to the optical properties of the lens [10].

Associations of BFSP1 with chemical compounds

• Filensin represents a membrane-associated element, resistant to salt and nonionic detergent treatment, and extractable only by alkali or high concentrations of urea [7].
• Purified filensin binds to PI, a synthetic peptide modelled after a segment of the COOH-terminal domain of peripherin (a type III intermediate filament protein highly homologous to vimentin), but not to various other peptides including the NH2-terminal headpiece of vimentin and derivatives of its middle (rod) domain [7].
• Filensin behaves as a ureaextractable, hydrophilic protein which does not partition with Triton X-114 and is not affected by 1 M hydroxylamine at alkaline pH, an agent known to release fatty-acylated proteins from the membrane [13].
• The involvement of chelatable iron in the oxygen-sensing mechanism was confirmed by the abolition of the DFO and CP-94 survival effect by Fe(2+) ions [1].
• The hydroxypyranone ethylmaltol has been compared with the 3-hydroxypyridin-4-one CP94 and to its structurally related lipophilic analogue CP25 as well as with the 3-hydroxypyridin-2-one, CP02 [14].

Other interactions of BFSP1

• The results obtained with MBP-alphaB were confirmed by immunoprecipitation reactions in which immunoprecipitation of native bovine alphaB-crystallin from heat-shocked lens cell homogenates resulted in the coprecipitation of phakinin and filensin [15].
• Immunoelectron microscopy confirmed that filensin and AQP0 were present in the same membrane compartments [9].
• Filensin: a new vimentin-binding, polymerization-competent, and membrane-associated protein of the lens fiber cell [7].
• The first seven genes consist of structural molecules, and the second half of genes are composed of heat shock proteins, filensin, and glutathione peroxidase 3 [16].
• We found that the LEP503, MIP and Filensin promoters induced strong lens-specific expression of a reporter gene, in human lens cells [17].

Analytical, diagnostic and therapeutic context of BFSP1

• We have used the polymerase chain reaction (PCR) to amplify CP 115 and CP 47 encoding sequences from human lens cDNA samples [8].
• Since the BFSP1 that encodes the lens-specific beaded filament structural protein 1 (filensin) has been mapped around the CPP3 region, we performed sequence analysis on its entire coding region [18].
• Confocal microscopy on frozen lens sections reveals that phakinin colocalizes with filensin and is distributed along the periphery of the lens fiber cells [6].
• Using cosedimentation assays, flotation assays and immunoelectron microscopy, we have examined the properties of purified filensin and measured its binding to lens membranes [13].
• Northern blot analysis was used to assess mRNA levels for CP49, filensin, and gammaS-crystallin (control) [19].

References