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POLD4  -  polymerase (DNA-directed), delta 4,...

Homo sapiens

Synonyms: DNA polymerase delta subunit 4, DNA polymerase delta subunit p12, POLDS, p12
 
 
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Disease relevance of POLD4

  • Of the various phosphorylated forms of p12 protein purified from virions, only a species containing relatively little phosphate can bind in vitro to purified homologous 70S viral RNA [1].
  • The purified p12 phosphoprotein of Rauscher murine leukemia virus was fractionated by ion exchange chromatography into subpopulations of molecules containing different amounts of covalently linked phosphate [1].
  • Unlike experimentally induced virus-negative leukaemias and sarcomas of other species, LSA cells from FeLV-negative LSA cats lack any FeLV proteins, including p15 or p12, and complete functional copies of FeLV provirus and thus do not produce FeLV when grown in cell culture [2].
  • The same two DNA segments are also included in the distal p13-p14.1 deletion of another patient, who has aniridia, Wilms' tumor, and hypogonadism, but they are not included in the p12-p13 deletion of a third patient, who does not have aniridia but has had a Wilms' tumor [3].
  • Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome [4].
 

Psychiatry related information on POLD4

 

High impact information on POLD4

  • The results show that phosphorylation of type C viral p12 proteins influences the extent, but not the specificity, of their interaction with homologous viral RNA [1].
  • Similar experiments show that the major phosphoproteins of mammalian type C viruses (p12 for murine viruses and p16 for endogenous primate viruses) are also the specific RNA binding proteins and, similarly, are found closely associated with the 70S RNA genomes in the intact viral particles [6].
  • Using ultraviolet irradiation to stabilize ribonucleoprotein complexes in intact virions, the same molecular species of p12 phosphoprotein can be isolated in close association with the 70S viral genome [1].
  • The alpha 2 and beta genes are both located on chromosome 4 in bands p12-p13 and may be adjacent [7].
  • Of the normal diploid B-lymphoblast cultures exposed to type C viruses, 12 were tested for the presence of viral RNA and structural proteins (p12, p30, gp70), and this information was correlated with tumorigenicity [8].
 

Chemical compound and disease context of POLD4

 

Biological context of POLD4

 

Anatomical context of POLD4

  • In addition to these activators, the bovine leukemia virus (BLV) and the human T-cell leukemia virus (HTLV) contain alternative open reading frames (R3 and G4 for BLV; p30, p13, and p12 for HTLV) [17].
  • Clones from this library have been mapped on a panel of human-rodent somatic cell hybrids that divides the region from distal p12 to proximal p14 into seven physical intervals, A total of 1500 clones has been isolated, 250 clones have been characterized, and 58 clones have been mapped [18].
  • Feline sarcoma virus (FeSV) rescued from transformed nonproducer mink or rat cells contains two FeSV-specific antigens (p15 and p12), and the feline oncornavirus-associated cell membrane antigen (FOCMA) [19].
  • In addition, the proteolytic cleavage of CPP32 resulting in the formation of two active fragments (p17 and p12) was observed in cytosolic extracts from TPEN-treated Jurkat cells, but not in extracts which were prepared from cells treated with TPEN in the presence of VADcmk or DEVD-CHO [20].
  • Furthermore, human pancreas expressed an additional previously unrecognized splice variant of INK4a, termed p12, through the use of an alternative splice donor site within intron 1 [21].
 

Associations of POLD4 with chemical compounds

  • To determine its role in replication, we introduced a series of deletion and alanine-scanning substitution mutations throughout the p12 coding region of a proviral DNA, and characterized the phenotypes of the resulting mutant viruses [14].
  • Purified, detergent-soluble HLA antigens (p44,12) are composed of a glycoprotein of molecular weight 44,000 (p44) and a peptide of molecular weight 12,000 (p12), beta2-microglobulin [22].
  • Peptide maps of these fragments were compared to maps of p15, p12, and three CNBr fragments of p30 [23].
  • These data supports the possibility that p25 is a homodimeric form of p12 through the cysteine residue [24].
  • The p20/p12 processing pattern of procaspase-3 in our model points to GrB, the sole serine protease with caspase activity [25].
 

Analytical, diagnostic and therapeutic context of POLD4

  • Molecular cloning and sequencing of this DNA showed that the pol and env genes have been deleted, but that the complete gag region has been conserved and has a novel sequence encoding the p12 protein [26].
  • Immunoprecipitation with specific sera shows that P120 contains regions homologous to the 5'-terminal segment of the MULV gag gene complex--p15, p12, and at least part of p30--but lacks detectable determinants of p10, reverse transcriptase, and the envelope glycoprotein [27].
  • By using radioimmunoassays developed for each polypeptide, it was possible to demonstrate that all three low molecular weight polypeptides, p15, p12, and p10, were immunologically unique [28].
  • The inter-subunit interactions of the p12 subunit were determined by yeast two-hybrid assays and by pulldown assays [29].
  • The gene was mapped to chromosome 3 p12-p11 by Radiation Hybrid Panel analysis [30].

References

  1. Phosphorylation of murine type C viral p12 proteins regulates their extent of binding to the homologous viral RNA. Sen, A., Sherr, C.J., Todaro, G.J. Cell (1977) [Pubmed]
  2. Development of virus non-producer lymphosarcomas in pet cats exposed to FeLv. Hardy, W.D., McClelland, A.J., Zuckerman, E.E., Snyder, H.W., MacEwen, E.G., Francis, D., Essex, M. Nature (1980) [Pubmed]
  3. Two anonymous DNA segments distinguish the Wilms' tumor and aniridia loci. Davis, L.M., Stallard, R., Thomas, G.H., Couillin, P., Junien, C., Nowak, N.J., Shows, T.B. Science (1988) [Pubmed]
  4. Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA. Prats, A.C., Sarih, L., Gabus, C., Litvak, S., Keith, G., Darlix, J.L. EMBO J. (1988) [Pubmed]
  5. Case report: autistic disorder and chromosomal abnormality 46, XX duplication (4) p12-p13. Sabaratnam, M., Turk, J., Vroegop, P. European child & adolescent psychiatry. (2000) [Pubmed]
  6. The genome-associated, specific RNA binding proteins of avian and mammalian type C viruses. Sen, A., Todaro, G.J. Cell (1977) [Pubmed]
  7. Chromosomal localization of GABAA receptor subunit genes: relationship to human genetic disease. Buckle, V.J., Fujita, N., Ryder-Cook, A.S., Derry, J.M., Barnard, P.J., Lebo, R.V., Schofield, P.R., Seeburg, P.H., Bateson, A.N., Darlison, M.G. Neuron (1989) [Pubmed]
  8. Effect of type C viral expression and cellular karyotype on human B-lymphoblast tumorigenicity in nude mice. Steuer, A.F., Ting, R.C., Markham, P.D., Salahuddin, Z., Gallo, R.C. J. Natl. Cancer Inst. (1982) [Pubmed]
  9. Cloning, bacterial expression, and characterization of the Mason-Pfizer monkey virus proteinase. Hrusková-Heidingsfeldová, O., Andreansky, M., Fábry, M., Bláha, I., Strop, P., Hunter, E. J. Biol. Chem. (1995) [Pubmed]
  10. Novel p19-related protein in Rous-associated virus type 61: implications for avian gag gene order. Shealy, D.J., Mosser, A.G., Rueckert, R.R. J. Virol. (1980) [Pubmed]
  11. Cooperative effect of gag proteins p12 and capsid during early events of murine leukemia virus replication. Lee, S.K., Nagashima, K., Hu, W.S. J. Virol. (2005) [Pubmed]
  12. Suppression of hematopoietic support function is associated with overexpression of interleukin-4 and transforming growth factor-beta 1 in LP-BM5 murine-leukemia-virus-infected stromal cell lines. Gallicchio, V.S., Tse, K.F., Morrow, J., Hughes, N.K. Acta Haematol. (1996) [Pubmed]
  13. Identification of a fourth subunit of mammalian DNA polymerase delta. Liu, L., Mo, J., Rodriguez-Belmonte, E.M., Lee, M.Y. J. Biol. Chem. (2000) [Pubmed]
  14. Mutations altering the moloney murine leukemia virus p12 Gag protein affect virion production and early events of the virus life cycle. Yuan, B., Li, X., Goff, S.P. EMBO J. (1999) [Pubmed]
  15. Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12. Board, P.G., Webb, G.C. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  16. Feline oncornavirus-associated cell membrane antigen: evidence for an immunologically crossreactive feline sarcoma virus-coded protein. Stephenson, J.R., Khan, A.S., Sliski, A.H., Essex, M. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  17. Attenuation of bovine leukemia virus by deletion of R3 and G4 open reading frames. Willems, L., Kerkhofs, P., Dequiedt, F., Portetelle, D., Mammerickx, M., Burny, A., Kettmann, R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. Somatic cell hybrid and long-range physical mapping of 11p13 microdissected genomic clones. Davis, L.M., Senger, G., Lüdecke, H.J., Claussen, U., Horsthemke, B., Zhang, S.S., Metzroth, B., Hohenfellner, K., Zabel, B., Shows, T.B. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  19. Pseudotypes of feline sarcoma virus contain an 85,000-dalton protein with feline oncornavirus-associated cell membrane antigen (FOCMA) activity. Sherr, C.J., Sen, A., Todaro, G.J., Sliski, A., Essex, M. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  20. The role of proteolysis in T cell apoptosis triggered by chelation of intracellular Zn2+. Jiang, S., Zhivotovsky, B., Burgess, D.H., Gahm, A., Chow, S.C., Orrenius, S. Cell Death Differ. (1997) [Pubmed]
  21. Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus. Robertson, K.D., Jones, P.A. Oncogene (1999) [Pubmed]
  22. Detergent-soluble HLA antigens contain a hydrophilic region at the COOH-terminus and a penultimate hydrophobic region. Springer, T.A., Strominger, J.L. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  23. Chemical determination of the m1 Moloney sarcoma virus pP60gag gene order: evidence for unique peptides in the carboxy terminus of the polyprotein. Oskarsson, M.K., Elder, J.H., Gautsch, J.W., Lerner, R.A., Vande Woude, G.F. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  24. Mutation of Cys105 inhibits dimerization of p12CDK2-AP1 and its growth suppressor effect. Kim, Y., Ohyama, H., Patel, V., Figueiredo, M., Wong, D.T. J. Biol. Chem. (2005) [Pubmed]
  25. Selective inhibition of dipeptidyl peptidase I, not caspases, prevents the partial processing of procaspase-3 in CD3-activated human CD8(+) T lymphocytes. Bidère, N., Briet, M., Dürrbach, A., Dumont, C., Feldmann, J., Charpentier, B., de Saint-Basile, G., Senik, A. J. Biol. Chem. (2002) [Pubmed]
  26. Severe immunodeficiency disease induced by a defective murine leukaemia virus. Aziz, D.C., Hanna, Z., Jolicoeur, P. Nature (1989) [Pubmed]
  27. Identification of an Abelson murine leukemia virus-encoded protein present in transformed fibroblast and lymphoid cells. Witte, O.N., Rosenberg, N., Paskind, M., Shields, A., Baltimore, D. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  28. Structural polypeptides of mammalian type C RNA viruses. Isolation and immunologic characterization of a low molecular weight polypeptide, p10. Barbacid, M., Stephenson, J.R., Aaronson, S.A. J. Biol. Chem. (1976) [Pubmed]
  29. Functional roles of p12, the fourth subunit of human DNA polymerase delta. Li, H., Xie, B., Zhou, Y., Rahmeh, A., Trusa, S., Zhang, S., Gao, Y., Lee, E.Y., Lee, M.Y. J. Biol. Chem. (2006) [Pubmed]
  30. Structure and polymorphisms of the human metabotropic glutamate receptor type 2 gene (GRM2): analysis of association with schizophrenia. Joo, A., Shibata, H., Ninomiya, H., Kawasaki, H., Tashiro, N., Fukumaki, Y. Mol. Psychiatry (2001) [Pubmed]
 
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