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Prg4  -  proteoglycan 4 (megakaryocyte stimulating...

Mus musculus

Synonyms: CACP, DOL54, JCAP, Lubricin, MSF, ...
 
 
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Disease relevance of Prg4

 

High impact information on Prg4

  • Prg4 began to be expressed in surface chondrocytes and synoviocytes after joint cavitation had occurred and remained strongly expressed by these cells postnatally [6].
  • Loss-of-function mutations in lubricin (a secreted glycoprotein encoded by the gene PRG4) cause the human autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) [6].
  • We conclude that lubricin has multiple functions in articulating joints and tendons that include the protection of surfaces and the control of synovial cell growth [6].
  • Here we report the isolation of a gene, DOL54, that is activated in primary fibroblasts by the expression of TLS-CHOP [1].
  • Antiserum generated against an epitope in the amino-terminal portion of lubricin detected protein in wild-type synovial fluid and in conditioned media from wild-type cultured synoviocytes [7].
 

Chemical compound and disease context of Prg4

 

Biological context of Prg4

  • Objectives and Methods: To identify novel chromosomal regions contributing to lung function, quantitative trait locus linkage analysis was applied in N(2) backcross and F(2) intercross mice derived from two inbred strains-C3H/HeJ and JF1/Msf-with extremely divergent phenotypes [9].
  • To obtain independent evidence for linkage and more precisely determine the location of the am3 locus, we generated EL/Sea congenic strains for am3 in which the restricted interval of chromosome 3 of EL/Sea was replaced by an MSM/Msf-derived homologue [10].
  • EL/Sea congenic mice that were either heterozygous or homozygous for the MSM/Msf-derived interval exhibited a significant decrease in the incidence of the absence of third molars, confirming previous genome scan results [10].
 

Anatomical context of Prg4

  • Interestingly, in contrast to wild-type lubricin, one disease-causing mutation that removes the last 8 amino acids of the protein, including a conserved cysteine residue, was not cleaved within the hemopexin-like domain when expressed in COS-7 cells [7].
  • Here we show using a combination of DNA binding assays, proteolytic clipping, and anti-Pax3 antibodies that MSF is indistinguishable from Pax3, a paired homeodomain transcription factor implicated genetically in melanocyte development and the regulation of the Mitf promoter [11].
  • This report describes the partial purification and characterization of mammary stimulating factor (MSF), a mitogenic peptide isolated from serum which initiates growth in mouse mammary epithelium [12].
  • The sitABCD feoB mutant (mutant SF) and the mntH sitABCD feoB mutant (mutant MSF) showed minimal Fe(II) uptake and were slightly impaired for replication in susceptible macrophages [13].
  • In as much as the human counterpart of lubricin is expressed in the thymic medulla of mice, the generation of knocked-out mice for its expression within the thymus could be one of the best models to test the above hypothesis [14].
 

Associations of Prg4 with chemical compounds

 

Analytical, diagnostic and therapeutic context of Prg4

References

  1. Induction of a secreted protein by the myxoid liposarcoma oncogene. Kuroda, M., Wang, X., Sok, J., Yin, Y., Chung, P., Giannotti, J.W., Jacobs, K.A., Fitz, L.J., Murtha-Riel, P., Turner, K.J., Ron, D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Expression of DOL54 is not restricted to myxoid liposarcomas with the FUS-DDIT3 chimera but is found in various sarcomas. Panagopoulos, I., Mertens, F., Isaksson, M., Mandahl, N. Oncol. Rep. (2004) [Pubmed]
  3. Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. Carreira, S., Dexter, T.J., Yavuzer, U., Easty, D.J., Goding, C.R. Mol. Cell. Biol. (1998) [Pubmed]
  4. TLS-CHOP target gene DOL54 expression in liposarcomas and malignant fibrous histiocytomas. Domoto, H., Hosaka, T., Oikawa, K., Ohbayashi, T., Ishida, T., Izumi, M., Iwaya, K., Toguchida, J., Kuroda, M., Mukai, K. Pathol. Int. (2002) [Pubmed]
  5. Mice protection with 2,4-monofurfurylidene-tetra-O-methyl-sorbitol (MSF) against acute toxicity due to Amanita phalloides. Zanoli, P., Poggioli, R., Sannicola Botticelli, C. Arzneimittel-Forschung. (1979) [Pubmed]
  6. The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. Rhee, D.K., Marcelino, J., Baker, M., Gong, Y., Smits, P., Lefebvre, V., Jay, G.D., Stewart, M., Wang, H., Warman, M.L., Carpten, J.D. J. Clin. Invest. (2005) [Pubmed]
  7. Consequences of disease-causing mutations on lubricin protein synthesis, secretion, and post-translational processing. Rhee, D.K., Marcelino, J., Al-Mayouf, S., Schelling, D.K., Bartels, C.F., Cui, Y., Laxer, R., Goldbach-Mansky, R., Warman, M.L. J. Biol. Chem. (2005) [Pubmed]
  8. Mechanism of protection with 2,4-monofurfurylidene-tetra-O-methyl sorbitol (MSF) against Amanita phalloides toxicity in mice. Zanoli, P. Arzneimittel-Forschung. (1979) [Pubmed]
  9. Genomewide linkage analysis identifies novel genetic Loci for lung function in mice. Reinhard, C., Meyer, B., Fuchs, H., Stoeger, T., Eder, G., Rüschendorf, F., Heyder, J., Nürnberg, P., de Angelis, M.H., Schulz, H. Am. J. Respir. Crit. Care Med. (2005) [Pubmed]
  10. Localization of am3 using EL congenic mouse strains. Shimizu, T., Han, J., Asada, Y., Okamoto, H., Maeda, T. J. Dent. Res. (2005) [Pubmed]
  11. Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter. Galibert, M.D., Yavuzer, U., Dexter, T.J., Goding, C.R. J. Biol. Chem. (1999) [Pubmed]
  12. Partial purification and characterization of mammary stimulating factor, a protein which promotes proliferation of mammary epithelium. Ptashne, K., Hsueh, H.W., Stockdale, F.E. Biochemistry (1979) [Pubmed]
  13. Acquisition of Mn(II) in addition to Fe(II) is required for full virulence of Salmonella enterica serovar Typhimurium. Boyer, E., Bergevin, I., Malo, D., Gros, P., Cellier, M.F. Infect. Immun. (2002) [Pubmed]
  14. Could rheumatoid arthritis result from an abnormal T cell response towards lubricin/superficial zone protein? Berthelot, J.M. Med. Hypotheses (2004) [Pubmed]
 
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