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Sox4  -  SRY (sex determining region Y)-box 4

Mus musculus

Synonyms: AA682046, Sox-4, Transcription factor SOX-4
 
 
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Disease relevance of Sox4

  • These defects lead to embryonic death at E14.5 and are similar to those observed in other mouse models of congenital heart disease, including Sox4 and Nfatc1 null embryos [1].
  • Among 13 myeloid leukemias induced by transplanting into mice bone marrow cells infected in vitro with a replication-defective retrovirus carrying the Sox4 oncogene, 9 contained insertional mutations at known or suspected cancer genes [2].
  • As previous studies in this laboratory had shown that the SOX4 gene was regulated by ovarian hormones in breast cancer cells, murine Sox4 expression was analyzed in the reproductive tissues of mice by Northern blot analysis and ribonuclease protection assays [3].
 

High impact information on Sox4

  • During murine embryogenesis, the transcriptional activator Sox-4 is expressed at several sites, but in adult mice expression is restricted to immature B and T lymphocytes [4].
  • This was a result of impaired development of the endocardial ridges (a specific site of Sox-4 expression) into the semilunar valves and the outlet portion of the muscular ventricular septum [4].
  • Sox-4, an Sry-like HMG box protein, is a transcriptional activator in lymphocytes [5].
  • Sox-4 was expressed in T and pre-B lymphocyte lines and in the murine thymus [5].
  • Sox-4 is thus the first 'classical' transcription factor in the Sox gene family with separable DNA-binding and transactivation domains [5].
 

Biological context of Sox4

 

Anatomical context of Sox4

  • Expression of Sox11 was found in the mesenchyme surrounding the pancreatic buds, whereas Sox4 and Sox9 were confined to the pancreatic epithelium and later to islets [9].
  • The transcription factor-encoding gene, Sox4, is expressed in a wide range of tissues and has been shown to be functionally involved in heart, B-cell and reproductive system development [6].
  • Roles of Sox4 in central nervous system development [6].
  • As development proceeded, their expression always appeared to relate to the maturational stage of the cell population, with Sox11 expression more transient than Sox4, except in the spinal cord where the reverse was true [6].
  • In contrast, Sox4 was detected broadly in the early pancreatic buds and eventually became restricted to the nuclei of all islet cells in the adult mouse [10].
 

Associations of Sox4 with chemical compounds

  • In contrast with observations on TCF-1 and LEF-1, cotransfection with Sox-4 unveiled a transactivating capacity, which mapped to its serine-rich C terminus [5].
  • Identification of cDNAs for Sox-4, an HMG-Box protein, and a novel human homolog of yeast splicing factor SSF-1 differentially regulated during apoptosis induced by prostaglandin A2/delta12-PGJ2 in Hep3B cells [11].
 

Other interactions of Sox4

  • We show here that several Sox transcription factors are expressed in the developing pancreas and in the islet, and that one of these factors, Sox4, is required for the normal development of pancreatic islets [10].
  • Sox4 cooperates with Evi1 in AKXD-23 myeloid tumors via transactivation of proviral LTR [12].
  • We reanalyzed AKXD-23 tumors for cooperating proviral insertion and found that each tumor had a proviral insertion in Sox4, which encodes an HMG-box transcription factor [12].
  • Co-expression of Ets-1 and Sox-4, but neither protein alone, was sufficient to activate the lck type l promoter in HeLa cells which do not normally express lck transcripts [13].
  • These results suggest that the expression of Sox-4 may be related to the apoptosis pathway leading to cell death as well as to tumorigenesis, and that Ssf-1 gene may serve as a negative regulator of PGA2/Delta12-PGJ2-mediated Hep3B cell apoptosis [11].
 

Analytical, diagnostic and therapeutic context of Sox4

  • Sox4-deficiency syndrome in mice is an animal model for common trunk [14].
  • Explanted fetal thymic organ cultures (FTOC) of Sox-4-deficient thymi yielded 10-50-fold fewer CD4 CD8 double-positive and single-positive cells than FTOC of littermates [15].
  • Interestingly, Sox-4 was highly expressed in subcutaneous tumors grown in nude mice as a xenograft from Hep3B cells [11].

References

  1. Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Wang, B., Weidenfeld, J., Lu, M.M., Maika, S., Kuziel, W.A., Morrisey, E.E., Tucker, P.W. Development (2004) [Pubmed]
  2. Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis. Du, Y., Spence, S.E., Jenkins, N.A., Copeland, N.G. Blood (2005) [Pubmed]
  3. Expression and hormonal regulation of the Sox4 gene in mouse female reproductive tissues. Hunt, S.M., Clarke, C.L. Biol. Reprod. (1999) [Pubmed]
  4. Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4. Schilham, M.W., Oosterwegel, M.A., Moerer, P., Ya, J., de Boer, P.A., van de Wetering, M., Verbeek, S., Lamers, W.H., Kruisbeek, A.M., Cumano, A., Clevers, H. Nature (1996) [Pubmed]
  5. Sox-4, an Sry-like HMG box protein, is a transcriptional activator in lymphocytes. van de Wetering, M., Oosterwegel, M., van Norren, K., Clevers, H. EMBO J. (1993) [Pubmed]
  6. Roles of Sox4 in central nervous system development. Cheung, M., Abu-Elmagd, M., Clevers, H., Scotting, P.J. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  7. SRY-related (Sox) genes in the genome of European Atlantic sturgeon (Acipenser sturio). Hett, A.K., Ludwig, A. Genome (2005) [Pubmed]
  8. Conservation of Sox4 gene structure and expression during chicken embryogenesis. Maschhoff, K.L., Anziano, P.Q., Ward, P., Baldwin, H.S. Gene (2003) [Pubmed]
  9. Expression of Sox transcription factors in the developing mouse pancreas. Lioubinski, O., Müller, M., Wegner, M., Sander, M. Dev. Dyn. (2003) [Pubmed]
  10. The HMG Box Transcription Factor Sox4 Contributes to the Development of the Endocrine Pancreas. Wilson, M.E., Yang, K.Y., Kalousova, A., Lau, J., Kosaka, Y., Lynn, F.C., Wang, J., Mrejen, C., Episkopou, V., Clevers, H.C., German, M.S. Diabetes (2005) [Pubmed]
  11. Identification of cDNAs for Sox-4, an HMG-Box protein, and a novel human homolog of yeast splicing factor SSF-1 differentially regulated during apoptosis induced by prostaglandin A2/delta12-PGJ2 in Hep3B cells. Ahn, S.G., Cho, G.H., Jeong, S.Y., Rhim, H., Choi, J.Y., Kim, I.K. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  12. Sox4 cooperates with Evi1 in AKXD-23 myeloid tumors via transactivation of proviral LTR. Boyd, K.E., Xiao, Y.Y., Fan, K., Poholek, A., Copeland, N.G., Jenkins, N.A., Perkins, A.S. Blood (2006) [Pubmed]
  13. An alternative pathway for expression of p56lck from type I promoter transcripts in colon carcinoma. McCracken, S., Kim, C.S., Xu, Y., Minden, M., Miyamoto, N.G. Oncogene (1997) [Pubmed]
  14. Sox4-deficiency syndrome in mice is an animal model for common trunk. Ya, J., Schilham, M.W., de Boer, P.A., Moorman, A.F., Clevers, H., Lamers, W.H. Circ. Res. (1998) [Pubmed]
  15. Sox-4 facilitates thymocyte differentiation. Schilham, M.W., Moerer, P., Cumano, A., Clevers, H.C. Eur. J. Immunol. (1997) [Pubmed]
 
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