The 3' untranslated region of the chicken c-src protooncogene modulates gene expression.

Tight regulation of the Src tyrosine kinase activity is essential for a variety of cellular processes, namely transitions of the cell cycle. The peaks of Src activity are dependent on its posttranslational modifications as well as on the regulation of gene expression. The 3'UTRs of mRNAs are often crucial for rapid changes of the protein level. The chicken c-src 3'UTR effects on gene expression have been explored. The c-src 3'UTR decreased the in vivo tumorigenic potential of the src-activated mutants in chickens. This corresponds with the finding that the c-src 3'UTR reduced the Src protein and src mRNA levels and luciferase activity in vitro. Our results suggest that the chicken c-src 3'UTR plays a role in the negative control of gene expression, either transcriptionally or posttranscriptionally.

[1]  J. Plachy,et al.  Tumor induction by the LTR, v-src, LTR DNA in four B (MHC) congenic lines of chickens , 1992, Immunogenetics.

[2]  J. Plachy,et al.  src-specific immunity in inbred chickens bearing v-src DNA- and RSV-induced tumors , 2004, Immunogenetics.

[3]  B. Deroo,et al.  Proteasome Inhibitors Reduce Luciferase and β-Galactosidase Activity in Tissue Culture Cells* , 2002, The Journal of Biological Chemistry.

[4]  R. Schneider,et al.  Ubiquitin-dependent mechanism regulates rapid turnover of AU-rich cytokine mRNAs , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Siedlecki,et al.  Regulatory functions of 3'UTRs. , 2001, Biochemical and biophysical research communications.

[6]  C. Gissi,et al.  Structural and functional features of eukaryotic mRNA untranslated regions. , 2001, Gene.

[7]  D. Elleder,et al.  CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Dehm,et al.  SRC transcriptional activation in a subset of human colon cancer cell lines , 2001, FEBS letters.

[9]  S. Dehm,et al.  An Alternative, Human SRC Promoter and Its Regulation by Hepatic Nuclear Factor-1α* , 2000, The Journal of Biological Chemistry.

[10]  T. Yeatman,et al.  Role of Src expression and activation in human cancer , 2000, Oncogene.

[11]  E. Raz,et al.  Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism , 2000, Nature Biotechnology.

[12]  S. Ritchie,et al.  Transcription of the Human c-Src Promoter Is Dependent on Sp1, a Novel Pyrimidine Binding Factor SPy, and Can Be Inhibited by Triplex-forming Oligonucleotides* , 2000, The Journal of Biological Chemistry.

[13]  Santhosh K. P. Kumar,et al.  Ubiquitin-mediated degradation of active Src tyrosine kinase. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Y. Hakak,et al.  Ubiquitin-dependent degradation of active Src , 1999, Current Biology.

[15]  C. Y. Chen,et al.  Unraveling a cytoplasmic role for hnRNP D in the in vivo mRNA destabilization directed by the AU-rich element. , 1999, Genes & development.

[16]  R. Cuesta,et al.  Control of mRNA decay by heat shock-ubiquitin-proteasome pathway. , 1999, Science.

[17]  H. Schmid,et al.  Possible Involvement of Proteasomes (Prosomes) in AUUUA-mediated mRNA Decay* , 1999, The Journal of Biological Chemistry.

[18]  Timothy J. Yeatman,et al.  Activating SRC mutation in a subset of advanced human colon cancers , 1999, Nature Genetics.

[19]  A. Shyu,et al.  RNA stabilization by the AU‐rich element binding protein, HuR, an ELAV protein , 1998, The EMBO journal.

[20]  J. Steitz,et al.  Overexpression of HuR, a nuclear–cytoplasmic shuttling protein, increases the in vivo stability of ARE‐containing mRNAs , 1998, The EMBO journal.

[21]  C. Demaria,et al.  Identification of AUF1 (heterogeneous nuclear ribonucleoprotein D) as a component of the alpha-globin mRNA stability complex , 1997, Molecular and cellular biology.

[22]  C. Vaquero,et al.  Regulation of p56lckMessenger Turnover upon T Cell Activation: Involvement of the 3′ Untranslated Region in Stability as Determined in Cell-free Extracts☆ , 1997 .

[23]  J. Plachy,et al.  Phenotypic changes induced by wild type and variant c-src genes carrying C-terminal sequence alterations. , 1996, Oncogene.

[24]  T. Hunter,et al.  Requirement for c-Src Catalytic Activity and the SH3 Domain in Platelet-derived Growth Factor BB and Epidermal Growth Factor Mitogenic Signaling* , 1996, The Journal of Biological Chemistry.

[25]  S. Courtneidge,et al.  The Src SH3 Domain Is Required for DNA Synthesis Induced by Platelet-derived Growth Factor and Epidermal Growth Factor* , 1996, The Journal of Biological Chemistry.

[26]  J. Plachy,et al.  Influence of the transduced 3'UTR of the c-src oncogene on tumour growth induced by the v-src gene of avian sarcoma virus PR2257. , 1996, The Journal of general virology.

[27]  S. Fumagalli,et al.  Requirement for Src family protein tyrosine kinases in G2 for fibroblast cell division. , 1995, Science.

[28]  J. Keene,et al.  Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[29]  G. Calothy,et al.  Origin and evolution of the c-src-transducing avian sarcoma virus PR2257. , 1994, The Journal of general virology.

[30]  G. Calothy,et al.  The 3' region of c-src gene mRNA is entirely included in exon 12 and does not encode another protein. , 1994, Biochimica et biophysica acta.

[31]  J. Keene,et al.  Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. , 1993, Molecular and cellular biology.

[32]  G. Calothy,et al.  Transduction of the cellular src gene and 3' adjacent sequences in avian sarcoma virus PR2257 , 1989, Journal of virology.

[33]  J. Plachy,et al.  Prague inbred lines of chickens: a biological model for MHC research. , 1989, Folia biologica.

[34]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[35]  P. Amouyel,et al.  Characterization of a MH2 mutant lacking the v-myc oncogene. , 1986, Virology.

[36]  G. Shaw,et al.  A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation , 1986, Cell.

[37]  B. Beutler,et al.  Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Y. Fujisawa,et al.  Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity. , 1984, Journal of the National Cancer Institute.

[39]  G. Calothy,et al.  Transformation of Chick Embryo Neuroretinal Cells by Rous Sarcoma Virus in vitro: Induction of Cell Proliferation , 1974, Science.