Disease relevance of RPA4

• The lack of cleavage of p60 is in contrast to the properties of p30 precursors detected in cells containing replicating avian or mammalian RNA tumor viruses [1].
• It was previously demonstrated that the 60,000 dalton (p60) precursor-like polyprotein containing murine p30 was a constituent of the feline leukemia virus pseudotype of Moloney sarcoma virus [m1MSV(FeLV)] [1].
• There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS) [2].
• The varions have properties of known type C RNA tumor viruses and share antigenic determinants with the major interspecies-specific antigen (p30) of simian sarcoma virus [3].
• We report that during activation of the simian virus 40 (SV40) pre-replication complex, SV40 T antigen (Tag) helicase actively loads replication protein A (RPA) on emerging single-stranded DNA (ssDNA) [4].

Psychiatry related information on RPA4

• A sensitive sandwich enzyme immunoassay for gamma-seminoprotein (p30, prostate-specific antigen) is described for sex discrimination of blood and bloodstains [5].

High impact information on RPA4

• Phosphorylation of RPA may play a role in coordinating DNA metabolism in the cell [6].
• In cells, RPA is phosphorylated by DNA-dependent protein kinase when RPA is bound to single-stranded DNA (during S phase and after DNA damage) [6].
• RPA may also have a role in modulating gene expression [6].
• We describe an enzyme-linked immunosorbent assay for a semen glycoprotein of prostatic origin, designated p30 [7].
• However, the antigen cannot be detected in body fluids from women, including vaginal fluid and urine, suggesting that p30 may be a male-specific antigen [7].

Chemical compound and disease context of RPA4

• Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y. This immunohistochemical study evaluates the specificity and sensitivity of MAb HBA71 for tumor diagnosis [8].
• Quantitative immunoelectrophoretic assay for murine oncornavirus p30: noncovalent facilitation by sodium dodecyl sulfate [9].
• In vitro cleavage of Pr65gag by the Moloney murine leukaemia virus proteolytic activity yields p30 whose NH2-terminal sequence is identical to virion p30 [10].
• Fluids from 208 follicles were analyzed with respect to the concentration of estradiol and progesterone and to the presence of RD 114 retrovirus p30-related protein (rp), assuming that such a protein indicates the presence of C-virus particles in the follicular fluids [11].

Biological context of RPA4

• Our results suggest that hyperphosphorylated RPA is preferentially localized to DSB repair and the DNA damage checkpoint complexes in response to DNA damage [12].
• RPA (replication protein A) is an essential factor for DNA DSB (double-strand break) repair and cell cycle checkpoint activation [12].
• These data point to the involvement of hRPA in regulation of telomere maintenance [13].
• Consistent with this prediction, transfections into the hematopoietic cell line Jurkat showed a 9.0- and 2.5-fold activation of the mim-1 promoter by the p32 and p30 isoforms, respectively [14].
• We found that two C/EBPepsilon isoforms, p32 and p30, possessing transcriptional activation domains were coexpressed in myeloid cells [14].

Anatomical context of RPA4

• Rpa4 is preferentially expressed in placental and colon mucosa tissues [15].
• In unirradiated HeLa cells, RPA-p34 is phosphorylated primarily at Ser-23 and Ser-29 [16].
• We conclude that the assay for p30 offers a more sensitive and specific method of semen detection in rape investigation than the enzyme assay for prostatic acid phosphatase [7].
• Antigens related to the major structural protein (p30) of type C viruses isolated from a woolly monkey and a gibbon ape were found in peripheral white blood cells from five patients with acute leukemia [17].
• Detection and immunochemical characterization of a primate type C retrovirus-related p30 protein in normal human placentas [18].

Associations of RPA4 with chemical compounds

• The additional 32 NH2-terminal residues made p32 a significantly more potent transcriptional activator than p30 [14].
• The disruption of the p30 gene caused the growth retardation of yeast cells in a glycerol medium but not in a glucose medium, i.e. the impairment of the mitochondrial ATP synthesis [19].
• C-1027 and neocarzinostatin doses that caused similar levels of DNA damage resulted in equivalent increases in RPA32 hyperphosphorylation and RPA nuclear retention and decreases in replication activity, suggesting a common response to enediyne-induced DNA damage [20].
• At least four of the eight serines and one threonine in the N-terminal 33 residues of RPA-p34 can become phosphorylated after UV irradiation [16].
• Peptide maps of 48,000-dalton CNBr fragments of m3 P70 and ml P60 were similar and suggested that both polyproteins were similar through the NH2-terminal two-thirds of p30 [21].

Regulatory relationships of RPA4

• Further mutational studies indicated that, although the N-terminal 32-amino acid peptide of C/EBPepsilon isoform p32 did not greatly influence the transactivation activity compared with p30 isoform, this peptide does modulate transactivation activity [22].

Other interactions of RPA4

• Among the nine polypeptides detected by immunoblotting, 38 recognized p14, 17 recognized p8, and 16 recognized p8, and 16 recognized p30 [23].
• The p30 isoform lacked significant transcriptional activity, suggesting that other hematopoietic-specific factors were required for its function [14].

Analytical, diagnostic and therapeutic context of RPA4

• Northern (RNA) blot analysis suggest that there are alternatively processed forms of the RPA4 mRNA, and Southern blot analysis indicates that beside RPA4 there may be other members of the RPA2 gene family [15].
• Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed [2].
• Three antisera against RD114 p30 gave similar positive results, while two antisera prepared against simian sarcoma virus p30, one antiserum prepared against murine leukemia virus p30, and one antiserum prepared against feline leukemia virus p30 gave no immunofluorescence [24].
• Tryptic peptide fingerprints of the p30 and gp70 structural elements of the viruses indicated that all of the known endogenous muLVs of BALB/c mice were present in the mixture [25].
• An antigen crossreacting with the 30,000-molecular-weight protein (p30) of the feline endogenous oncornavirus (RD114) was detected in a well-characterized human fibrosarcoma cell line, HT1080, by indirect immunofluorescence [24].

References