Disease relevance of PPFIBP1

• CONCLUSIONS: In the current study the authors identified genomic regions and new candidate genes (RPS6, CDK4, and PPFIBP1) that were associated with tumor progression and prognosis in patients with high-grade chondrosarcomas [1].
• A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue [2].
• The translation of 15-lipoxygenase (LOX) mRNA in erythroid precursor cells and of the L2 mRNA of human papilloma virus type 16 (HPV-16) in squamous epithelial cells is silenced when either of these cells is immature and is activated in maturing cells by unknown mechanisms [3].
• Three new members of this family have now been cloned and characterized, two proteins from Legionella pneumophila (L1 H-NOX and L2 H-NOX) and one from Nostoc punctiforme (Np H-NOX) [4].
• McCoy cells infected with Chlamydia trachomatis serovars E or L2 revealed, by indirect immunofluorescence microscopy, collocation of microtubules and Chlamydia-containing vesicles during the process of migration from the host cell surface to a perinuclear location [5].

High impact information on PPFIBP1

• During 6 months of treatment, the bone mineral density of the L2 to L4 vertebrae increased 3%; this value exceeded the coefficient of variation of this measurement [6].
• NO dissociation kinetics for L1 H-NOX and L2 H-NOX have been determined and support a model in which NO dissociates from the distal side of the heme in both 5- and 6-coordinate complexes [4].
• S100A4-liprin beta1 interaction resulted in the inhibition of liprin beta1 phosphorylation by both kinases in vitro [7].
• We mapped the S100A4 binding site at the C terminus of the liprin beta1 molecule between amino acid residues 938 and 1005 [7].
• Immunofluorescence staining demonstrated the co-localization of S100A4 and liprin beta1 in the cytoplasm and particularly at the protrusion sites of the plasma membrane [7].

Chemical compound and disease context of PPFIBP1

• Chlamydia trachomatis serovar L2 induces protein tyrosine phosphorylation during uptake by HeLa cells [8].
• Using synthetic peptides we have shown that positively charged sequences present at the C terminus of the L1 protein and the N and C termini of the L2 protein of human papillomavirus type 16 (HPV-16) bind to both DNA and heparan sulfate receptors [9].

Biological context of PPFIBP1

• Chromosome segment-specific cDNA array analysis of 29 expressed sequences within the whole interval between D12S1617 and sts-N38796 indicated overexpression of four ESTs, two corresponding to DEC2 and PPFIBP1, and two to ESTs with unknown function [10].
• The complete absence of the L1 domain reduced the enhancements of both of these activities but not the maximal effector-stimulated PDK activity through acetylation of L2 [11].
• These results indicate that aspects of both the nonproductive and productive phases of the viral life cycle occur normally in the absence of functional L2 [12].
• In addition, the polyadenylation factor CStF-64 was also found to interact specifically with the region in L2 located 174 nucleotides downstream of the early polyadenylation signal [13].
• mRNA instability elements in the human papillomavirus type 16 L2 coding region [14].

Anatomical context of PPFIBP1

• We have now used cell lines deficient for promyelocytic leukemia (PML) protein, the main structural component of ND10, to study the role of this nuclear protein for L2 incorporation into virus-like particles (VLPs) [15].
• In immunoblotting with anti-phosphotyrosine antibodies of C. trachomatis L2-infected HeLa cells, but not with uninfected cells, two rows of spots were observed with a molecular mass of 69 and 71 kDa and pI from 5.0 to 5 [16].
• The functional relationship between L1 and L2 lysosome subpopulations has been studied in cultured thyroid cells reassociated into follicles [17].
• Treatment of prelabelled thyroid cells with chloroquine and leupeptin induced the accumulation of immunoprecipitable 125I-thyroglobulin into a lysosome fraction corresponding to the L2 subpopulation [17].
• CONCLUSIONS: Keratoconus corneas have elevated levels of cathepsins V/L2, -B, and -G, which can stimulate hydrogen peroxide production, which, in turn, can upregulate catalase, an antioxidant enzyme [18].

Associations of PPFIBP1 with chemical compounds

• In the current study, we demonstrate that saturated (palmitic and myristic; 50 mum) fatty acids (FA) inhibit activity of the promoter of the major (L2) transcript of the GH receptor gene; unsaturated (oleic and linoleic) FA (200 mum) do not alter activity of the promoter [19].
• We have previously shown that C. trachomatis L2 induces tyrosine phosphorylation of eukaryotic proteins upon their entry by phagocytosis [16].
• Furthermore, we demonstrate that a specific, highly conserved, histidine residue in the C-terminal region of L2 is essential for the function of the translational apparatus [20].
• Near 1 microM Ca(2+), tight binding of PDP1 but not PDP1c to gel-anchored L2 required Mg(2+) [21].
• The overall polypeptide composition of L, L1 and L2 analysed by polyacrylamide-gel electrophoresis was very similar, except for thyroglobulin which was more abundant in L2 than in either L or L1 [17].

Other interactions of PPFIBP1

• These findings indicate two target regions within the 3.5-Mb segment in 12p11-12, one proximal including PPFIBP1, and one distal including KRAS2 [10].

Analytical, diagnostic and therapeutic context of PPFIBP1

• We showed by the immunoprecipitation analysis that S100A4 interacts specifically with liprin beta1 in vivo [7].
• The L2 sequence was introduced by PCR (by replacing 13 codons) into sequences coding for L1 surface loops D-E (chideltaC-L2), E-F (chideltaA-L2), and an internal loop C-D (chideltaH-L2); into the h4 helix (chideltaF-L2); and between h4 and beta-J structural regions (chideltaE-L2) [22].
• The presence of inhibitory sequences in the L1 and L2 mRNAs may aid the virus in avoiding the host immunosurveillance and in establishing persistent infections [14].
• Isothermal titration calorimetry and (45)Ca(2+) binding studies failed to detect binding of Ca(2+) (<100 microM) to L2 or PDP1c, alone, but readily detected binding to L2 and PDP1c [21].
• Estradiol or levormeloxifene inhibited loss of lumbar spine bone mineral density (BMD) following ovariectomy compared with untreated monkeys (ovx -5.0%; sham -0.4%; est +0.2%; L1 -3.6%, L2 -2.0%, L3 -2.5%) [23].

References