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PMID: 8552074 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transcriptional down regulation of the nov proto-oncogene in fibroblasts transformed by p60v-src.

Molecular and cellular biology ·Vol. 16 ·No. 2 ·1996-02-00 ·Pages 481-6

Scholz G, Martinerie C, Perbal B, Hanafusa H

Abstract

We have sought to identify genes whose expression is altered as a consequence of transformation by p60v-src. Using the mRNA differential display method, we have identified the nov proto-oncogene as one gene that is down regulated in chicken embryo fibroblasts (CEFs) transformed by p60v-src. nov transcripts were also found to be present at only very low levels in proliferating CEFs in comparison with quiescent CEFs. Serum stimulation of quiescent CEFs also resulted in a decline in the steady-state level of nov transcripts. Taken together, these findings suggest that the nov gene is expressed only in quiescent fibroblasts and that its down regulation may contribute to cellular transformation by the v-src oncogene. Down regulation of the nov gene appears to occur at both the transcriptional and posttranscriptional levels. Results obtained from experiments with a protein kinase inhibitor suggest that protein kinase C may be a key downstream effector in mediating the down regulation of nov transcripts in response to activation of p60src or serum stimulation. In addition, we found that transcription of an unknown gene is required for the decline in the steady-state level of nov transcripts in response to serum stimulation.

MeSH Terms
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Animals Cell Division Cell Nucleus/metabolism Cell Transformation, Neoplastic/genetics Cells, Cultured Chickens Connective Tissue Growth Factor Down-Regulation Enzyme Inhibitors/pharmacology Fibroblasts/cytology Gene Expression Regulation, Neoplastic Immediate-Early Proteins Intercellular Signaling Peptides and Proteins Isoquinolines/pharmacology Kinetics Oncogene Protein pp60(v-src)/genetics Oncogene Proteins/biosynthesis,genetics Oncogene Proteins, Viral/biosynthesis,genetics Piperazines/pharmacology Protein Kinase C/antagonists & inhibitors Proto-Oncogene Proteins/biosynthesis,genetics RNA, Messenger/biosynthesis Transcription, Genetic
Chemicals
Enzyme Inhibitors Immediate-Early Proteins Intercellular Signaling Peptides and Proteins Isoquinolines Oncogene Proteins Oncogene Proteins, Viral Piperazines Proto-Oncogene Proteins RNA, Messenger Connective Tissue Growth Factor 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Oncogene Protein pp60(v-src) Protein Kinase C
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Scholz G
Laboratory of Molecular Oncology, Rockefeller University, New York, New York 10021, USA.
Martinerie C
Perbal B
Hanafusa H
References (48)
48 references, click to expand
  1. The membrane-binding domain and myristylation of p60v-src are not essential for stimulation of cell proliferation.
    J Virol. 1987 May;61(5):1678-81 PMID: 3106650
  2. Physical mapping of human loci homologous to the chicken nov proto-oncogene.
    Oncogene. 1992 Dec;7(12):2529-34 PMID: 1334251
  3. Molecular cloning and characterization of a cDNA showing negative regulation in v-src-transformed 3Y1 rat fibroblasts.
    Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2593-7 PMID: 8385338
  4. Transcriptional downregulation of the retina-specific QR1 gene by pp60v-src and identification of a novel v-src-responsive unit.
    Mol Cell Biol. 1993 Jun;13(6):3401-14 PMID: 8388536
  5. A turnover pathway for both stable and unstable mRNAs in yeast: evidence for a requirement for deadenylation.
    Genes Dev. 1993 Aug;7(8):1632-43 PMID: 8393418
  6. Structural analysis of the human nov proto-oncogene and expression in Wilms tumor.
    Oncogene. 1994 Sep;9(9):2729-32 PMID: 7520150
  7. c phosphorylation and activation of the IGF-I receptor in src-transformed cells.
    J Biol Chem. 1994 Nov 4;269(44):27315-21 PMID: 7525552
  8. Activation of YRP kinase by v-Src and protein kinase C-mediated signal transduction pathways.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2592-6 PMID: 7535926
  9. Contribution of MAV-1-induced nephroblastoma to the study of genes involved in human Wilms' tumor development.
    Crit Rev Oncog. 1994;5(6):589-613 PMID: 8519812
  10. Protein-tyrosine kinases.
    Annu Rev Biochem. 1985;54:897-930 PMID: 2992362
  11. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670-4 PMID: 2419912
  12. Activation of the transforming potential of p60c-src by a single amino acid change.
    Proc Natl Acad Sci U S A. 1986 Jun;83(12):4228-32 PMID: 2424022
  13. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation.
    Cell. 1986 Aug 29;46(5):659-67 PMID: 3488815
  14. Genetic lesions involved in temperature sensitivity of the src gene products of four Rous sarcoma virus mutants.
    J Virol. 1986 Dec;60(3):858-67 PMID: 3023675
  15. Transformation by Rous sarcoma virus induces a novel gene with homology to a mitogenic platelet protein.
    Cell. 1987 May 8;49(3):321-8 PMID: 3032449
  16. Genistein, a specific inhibitor of tyrosine-specific protein kinases.
    J Biol Chem. 1987 Apr 25;262(12):5592-5 PMID: 3106339
  17. Constitutive expression of a gene encoding a polypeptide homologous to biologically active human platelet protein in Rous sarcoma virus-transformed fibroblasts.
    Proc Natl Acad Sci U S A. 1987 Oct;84(19):6715-9 PMID: 2821543
  18. Cell transformation by the viral src oncogene.
    Annu Rev Cell Biol. 1987;3:31-56 PMID: 2446642
  19. Identification of a phorbol ester-repressible v-src-inducible gene.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1178-82 PMID: 2537491
  20. Phosphatidylinositol kinase activity associates with viral p60src protein.
    Mol Cell Biol. 1989 Apr;9(4):1651-8 PMID: 2542773
  21. Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton.
    J Cell Biol. 1989 Jun;108(6):2401-8 PMID: 2472406
  22. Rapid transformation of cells by Rous sarcoma virus.
    Proc Natl Acad Sci U S A. 1969 Jun;63(2):318-25 PMID: 4308272
  23. Fibrinolysis associated with oncogenic transformation. Partial purification and characterization of the cell factor, a plasminogen activator.
    J Biol Chem. 1974 Jul 10;249(13):4295-305 PMID: 4368727
  24. Temperature-sensitive expression of differentiation in transformed myoblasts.
    Nature. 1975 Apr 3;254(5499):429-31 PMID: 163986
  25. Effect of oncogenic virus on muscle differentiation.
    Proc Natl Acad Sci U S A. 1975 Oct;72(10):4051-5 PMID: 172892
  26. Use of recombinant plasmids to characterize collagen RNAs in normal and transformed chick embryo fibroblasts.
    J Biol Chem. 1979 Jun 25;254(12):4935-8 PMID: 221453
  27. Effects of transformation on fibronectin gene expression using cloned fibronectin cDNA.
    J Biol Chem. 1981 Jan 10;256(1):520-5 PMID: 6256355
  28. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7) is a selective inhibitor of protein kinase C in rabbit platelets.
    Biochem Biophys Res Commun. 1984 Nov 30;125(1):258-64 PMID: 6239622
  29. Gene regulation by tyrosine kinases: src protein activates various promoters, including c-fos.
    Mol Cell Biol. 1989 Jun;9(6):2493-9 PMID: 2474755
  30. Evidence that v-src and v-fps gene products use a protein kinase C-mediated pathway to induce expression of a transformation-related gene.
    Proc Natl Acad Sci U S A. 1989 Sep;86(18):7017-21 PMID: 2550927
  31. Processing of 9E3 mRNA and regulation of its stability in normal and Rous sarcoma virus-transformed cells.
    Mol Cell Biol. 1989 Nov;9(11):4738-45 PMID: 2557539
  32. A simplification of the nuclear run-off transcription assay.
    Biotechniques. 1989 Oct;7(9):942, 944 PMID: 2483664
  33. Serum and v-src increase the level of a CCAAT-binding factor required for transcription from a retroviral long terminal repeat.
    Genes Dev. 1990 Feb;4(2):243-54 PMID: 2159932
  34. Expression of cyr61, a growth factor-inducible immediate-early gene.
    Mol Cell Biol. 1990 Jul;10(7):3569-77 PMID: 2355916
  35. Constitutive phosphorylation of the receptor for insulinlike growth factor I in cells transformed by the src oncogene.
    Mol Cell Biol. 1990 Jul;10(7):3626-34 PMID: 2162477
  36. Association between the PDGF receptor and members of the src family of tyrosine kinases.
    Cell. 1990 Aug 10;62(3):481-92 PMID: 1696179
  37. Transcriptional regulation of the transforming growth factor beta 1 promoter by v-src gene products is mediated through the AP-1 complex.
    Mol Cell Biol. 1990 Sep;10(9):4978-83 PMID: 2117705
  38. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
    Cell. 1991 Feb 22;64(4):693-702 PMID: 1997203
  39. v-Src activates mitogen-responsive transcription factor Egr-1 via serum response elements.
    J Biol Chem. 1991 Jun 15;266(17):10802-6 PMID: 2040600
  40. Structure, mapping, and expression of fisp-12, a growth factor-inducible gene encoding a secreted cysteine-rich protein.
    Cell Growth Differ. 1991 May;2(5):225-33 PMID: 1888698
  41. Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.
    J Cell Biol. 1991 Sep;114(6):1285-94 PMID: 1654338
  42. Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas.
    Mol Cell Biol. 1992 Jan;12(1):10-21 PMID: 1309586
  43. MARCKS protein is transcriptionally down-regulated in v-Src-transformed BALB/c 3T3 cells.
    J Biol Chem. 1992 Jan 15;267(2):1327-30 PMID: 1370466
  44. Transcriptional activation of the CEF-4/9E3 cytokine gene by pp60v-src.
    Mol Cell Biol. 1992 Apr;12(4):1490-9 PMID: 1549106
  45. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192-6 PMID: 1594631
  46. Regulation of the junB gene by v-src.
    Mol Cell Biol. 1992 Aug;12(8):3356-64 PMID: 1630451
  47. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction.
    Science. 1992 Aug 14;257(5072):967-71 PMID: 1354393
  48. The cell cycle and c-Src.
    Curr Opin Genet Dev. 1993 Feb;3(1):26-34 PMID: 7680927
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.2.481
Published
1996-02-00
Pages
481-6
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231025
Subset
IM
Grants
NCI NIH HHS · CA44356 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.2.481 PMC Full Text View journal details
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