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PMID: 11250904 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis.

The EMBO journal ·Vol. 20 ·No. 6 ·2001-03-15 ·Pages 1383-93

Boon K, Caron HN, van Asperen R, Valentijn L, Hermus MC, van Sluis P, Roobeek I, Weis I, Voûte PA, Schwab M, Versteeg R

Abstract

The myc oncogenes are frequently activated in human tumors, but there is no comprehensive insight into the target genes and downstream cellular pathways of these transcription factors. We applied serial analysis of gene expression (SAGE) to identify targets of N-myc in neuroblastomas. Analysis of 42,000 mRNA transcript tags in SAGE libraries of N-myc- transfected and control neuroblastoma cells revealed 114 up-regulated genes. The majority of these genes have a role in ribosome assembly and activity. Northern blot analysis confirmed up-regulation of all tested transcripts. Induction was complete within 4 h after N-myc expression. The large majority of the ribosomal proteins were induced, as well as genes controlling rRNA maturation. Cellular rRNA content was 45% induced. SAGE libraries and northern blot analysis confirmed up-regulation of many of these genes in N-myc-amplified neuroblastomas. As N-myc can functionally replace c-myc, we analyzed whether N-myc targets were induced by c-myc as well. Approximately 40% of these N-myc targets were up-regulated in a c-myc-transfected melanoma cell line. These data suggest that myc genes function as major regulators of the protein synthesis machinery.

MeSH Terms
Gene Expression Profiling/methods Gene Expression Regulation, Neoplastic Gene Library Genes, myc/genetics Glycolysis/genetics Humans Melanoma, Experimental/genetics Neuroblastoma/genetics Protein Biosynthesis/genetics RNA, Messenger/genetics RNA, Ribosomal/biosynthesis Ribosomal Proteins/biosynthesis,genetics Ribosomes/genetics Time Factors Up-Regulation
Chemicals
RNA, Messenger RNA, Ribosomal Ribosomal Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Boon K
Department of Human Genetics, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
Caron H N
van Asperen R
Valentijn L
Hermus M C
van Sluis P
Roobeek I
Weis I
Voûte P A
Schwab M
Versteeg R
References (43)
43 references, click to expand
  1. Structure and functions of nucleolin.
    J Cell Sci. 1999 Mar;112 ( Pt 6):761-72 PMID: 10036227
  2. c-Myc target genes involved in cell growth, apoptosis, and metabolism.
    Mol Cell Biol. 1999 Jan;19(1):1-11 PMID: 9858526
  3. Mysterious liaisons: the relationship between c-Myc and the cell cycle.
    Oncogene. 1999 May 13;18(19):2934-41 PMID: 10378690
  4. A public database for gene expression in human cancers.
    Cancer Res. 1999 Nov 1;59(21):5403-7 PMID: 10554005
  5. c-Myc enhances protein synthesis and cell size during B lymphocyte development.
    Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13180-5 PMID: 10557294
  6. Myc induces the nucleolin and BN51 genes: possible implications in ribosome biogenesis.
    Nucleic Acids Res. 2000 Jan 15;28(2):446-53 PMID: 10606642
  7. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3260-5 PMID: 10737792
  8. N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation.
    Genes Dev. 2000 Jun 1;14(11):1390-9 PMID: 10837031
  9. Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo.
    Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11198-202 PMID: 11005843
  10. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins.
    Nature. 2000 Oct 5;407(6804):592-8 PMID: 11034201
  11. The human transcriptome map: clustering of highly expressed genes in chromosomal domains.
    Science. 2001 Feb 16;291(5507):1289-92 PMID: 11181992
  12. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour.
    Nature. 1983 Sep 15-21;305(5931):245-8 PMID: 6888561
  13. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.
    N Engl J Med. 1985 Oct 31;313(18):1111-6 PMID: 4047115
  14. N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma.
    Cell. 1986 Dec 5;47(5):667-74 PMID: 3096575
  15. The myc oncogene: its role in transformation and differentiation.
    Annu Rev Genet. 1986;20:361-84 PMID: 3028245
  16. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  17. c-myc down-regulates class I HLA expression in human melanomas.
    EMBO J. 1988 Apr;7(4):1023-9 PMID: 3402430
  18. Major nucleolar proteins shuttle between nucleus and cytoplasm.
    Cell. 1989 Feb 10;56(3):379-90 PMID: 2914325
  19. The role of c-myc in cellular growth control.
    Oncogene. 1999 May 13;18(19):2988-96 PMID: 10378694
  20. Drosophila myc regulates cellular growth during development.
    Cell. 1999 Sep 17;98(6):779-90 PMID: 10499795
  21. Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1).
    EMBO J. 1999 Oct 1;18(19):5310-20 PMID: 10508164
  22. Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27.
    EMBO J. 1999 Oct 1;18(19):5321-33 PMID: 10508165
  23. The MYC protein activates transcription of the alpha-prothymosin gene.
    EMBO J. 1991 Jan;10(1):133-41 PMID: 1989881
  24. Determination of the DNA sequence recognized by the bHLH-zip domain of the N-Myc protein.
    Nucleic Acids Res. 1992 May 11;20(9):2257-63 PMID: 1594445
  25. Myc and Max function as a nucleoprotein complex.
    Curr Opin Genet Dev. 1992 Apr;2(2):227-35 PMID: 1638116
  26. Increased expression of eukaryotic translation initiation factors eIF-4E and eIF-2 alpha in response to growth induction by c-myc.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6175-8 PMID: 8327497
  27. The ornithine decarboxylase gene is a transcriptional target of c-Myc.
    Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804-8 PMID: 8356088
  28. A protein complex required for signal-sequence-specific sorting and translocation.
    Nature. 1994 Aug 11;370(6489):434-40 PMID: 8047162
  29. Deletion mapping in neuroblastoma cell lines suggests two distinct tumor suppressor genes in the 1p35-36 region, only one of which is associated with N-myc amplification.
    Oncogene. 1995 Jan 19;10(2):291-7 PMID: 7838528
  30. Serial analysis of gene expression.
    Science. 1995 Oct 20;270(5235):484-7 PMID: 7570003
  31. Identification of a Myc-dependent step during the formation of active G1 cyclin-cdk complexes.
    EMBO J. 1995 Oct 2;14(19):4814-26 PMID: 7588611
  32. Proteins of the Myc network: essential regulators of cell growth and differentiation.
    Adv Cancer Res. 1996;68:109-82 PMID: 8712067
  33. Immunofluorescence studies of human fibroblasts demonstrate the presence of the complex of elongation factor-1 beta gamma delta in the endoplasmic reticulum.
    J Cell Sci. 1996 May;109 ( Pt 5):1113-7 PMID: 8743958
  34. An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc.
    Mol Cell Biol. 1996 Sep;16(9):4754-64 PMID: 8756633
  35. Conditional expression of N-myc in human neuroblastoma cells increases expression of alpha-prothymosin and ornithine decarboxylase and accelerates progression into S-phase early after mitogenic stimulation of quiescent cells.
    Oncogene. 1996 Aug 15;13(4):803-12 PMID: 8761302
  36. Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo.
    EMBO J. 1996 Aug 15;15(16):4344-57 PMID: 8861962
  37. Characterization of the yeast transcriptome.
    Cell. 1997 Jan 24;88(2):243-51 PMID: 9008165
  38. Myc versus USF: discrimination at the cad gene is determined by core promoter elements.
    Mol Cell Biol. 1997 May;17(5):2529-37 PMID: 9111322
  39. Gene expression profiles in normal and cancer cells.
    Science. 1997 May 23;276(5316):1268-72 PMID: 9157888
  40. Targeted expression of MYCN causes neuroblastoma in transgenic mice.
    EMBO J. 1997 Jun 2;16(11):2985-95 PMID: 9214616
  41. Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.
    Cell Growth Differ. 1997 Oct;8(10):1039-48 PMID: 9342182
  42. Nucleolin functions in the first step of ribosomal RNA processing.
    EMBO J. 1998 Mar 2;17(5):1476-86 PMID: 9482744
  43. MycN sensitizes neuroblastoma cells for drug-induced apoptosis.
    Oncogene. 1999 Feb 18;18(7):1479-86 PMID: 10050884
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.6.1383
Published
2001-03-15
Pages
1383-93
Language
English
Region
England
NLM ID
8208664
PMCID
PMC145518
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.6.1383 PMC Full Text View journal details
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