Skip to main content
SpringerLink
Log in

Myc Target Transcriptomes

  • Chapter
The Myc/Max/Mad Transcription Factor Network

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 302))

Abstract

The c-Myc oncogenic transcription factor plays a central role in many human cancers through the regulation of gene expression. Although the molecular mechanisms by which c-Myc and its obligate partner, Max, regulate gene expression are becoming better defined, genes or transcriptomes that c-Myc regulate are just emerging from a variety of different experimental approaches. Studies of individual c-Myc target genes and their functional implications are now complemented by large surveys of c-Myc target genes through the use of subtraction cloning, DNA microarray analysis, serial analysis of gene expression (SAGE), chromatin immunoprecipitation, and genome marking methods. To fully appreciate the differences between physiological c-Myc function in normal cells and deregulated c-Myc function in tumors, the challenge now is to determine how the authenticated transcriptomes effect the various phenotypes induced by c-Myc and to define how c-Myc transcriptomes are altered by the Mad family of proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arabi A, Wu S, Shiue C, Ridderstrale K, Larsson L-G, Wright APH (2005) c-Myc associates with ribosomal DNA in the nucleolus and activates RNA polymerase I transcription. Nat Cell Biol 7:303–310

    Article  PubMed  CAS  Google Scholar 

  • Ayer DE, Eisenman RN (1993) A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes Dev 7:2110–2119

    PubMed  CAS  Google Scholar 

  • Ayer DE, Lawrence QA, Eisenman RN (1995) Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell 80:767–776

    Article  PubMed  CAS  Google Scholar 

  • Barr LF, Campbell SE, Bochner BS, Dang CV (1998) Association of the decreased expression of alpha3beta1 integrin with the altered cell: environmental interactions and enhanced soft agar cloning ability of c-myc-overexpressing small cell lung cancer cells. Cancer Res 58:5537–5545

    PubMed  CAS  Google Scholar 

  • Bello-Fernandez C, Packham G, Cleveland JL (1993) The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proc Natl Acad Sci U S A 90:7804–7808

    PubMed  CAS  Google Scholar 

  • Benaud CM, Dickson RB (2001) Regulation of the expression of c-Myc by beta1 integrins in epithelial cells. Oncogene 20:759–768

    Article  PubMed  CAS  Google Scholar 

  • Boon K, Caron HN, van Asperen R, Valentijn L, Hermus MC, van Sluis P, Roobeek I, Weis I, Voute PA, Schwab M, Versteeg R (2001) N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis. EMBO J 20:1383–1393

    Article  PubMed  CAS  Google Scholar 

  • Bowen H, Biggs TE, Baker ST, Phillips E, Perry VH, Mann DA, Barton CH (2002) c-Myc represses the murine Nramp1 promoter. Biochem Soc Trans 30:774–777

    Article  PubMed  CAS  Google Scholar 

  • Bush A, Mateyak M, Dugan K, Obaya A, Adachi S, Sedivy J, Cole M (1998) c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets. Genes Dev 12:3797–3802

    PubMed  CAS  Google Scholar 

  • Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A, Sementchenko V Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras TR (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116:499–509

    Article  PubMed  CAS  Google Scholar 

  • Claassen GF, Hann SR (2000) Arole for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta-induced cell-cycle arrest. Proc Natl Acad Sci U S A 97:9498–9503

    Article  PubMed  CAS  Google Scholar 

  • Coller HA, Grandori C, Tamayo P, Colbert T, Lander ES, Eisenman RN, Golub TR (2000) 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 97:3260–3265

    Article  PubMed  CAS  Google Scholar 

  • D’Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, Cox JD, Ha SI, Belka GK, Golant A, et al (2001) c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 7:235–239

    Article  PubMed  CAS  Google Scholar 

  • Eilers M, Picard D, Yamamoto KR, Bishop JM (1989) Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells. Nature 340:66–68

    Article  PubMed  CAS  Google Scholar 

  • Felsher DW, Bishop JM (1999) Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc Natl Acad Sci U S A 96:3940–3944

    Article  PubMed  CAS  Google Scholar 

  • Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B (2003) Genomic targets of the human c-Myc protein. Genes Dev 17:1115–1129

    Article  PubMed  CAS  Google Scholar 

  • Fox EJ, Wright SC (2001) S-phase-specific expression of the Mad3 gene in proliferating and differentiating cells. Biochem J 359:361–367

    Article  PubMed  CAS  Google Scholar 

  • Frye M, Gardner C, Li ER, Arnold I, Watt FM (2003) Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. Development 130:2793–2808

    Article  PubMed  CAS  Google Scholar 

  • Grandori C, Gomez-Roman N, Felton-Edkins ZA Ngouenet C, Galloway DA, Eisenman RN and White RJ (2005) c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7:311–318

    Article  PubMed  CAS  Google Scholar 

  • Grewal SS, Li L, Orian A, Eisenman RN, Edgar BA (2005) Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol 7:295–302

    Article  PubMed  CAS  Google Scholar 

  • Guo QM, Malek RL, Kim S, Chiao C, He M, Ruffy M, Sanka K, Lee NH, Dang CV, Liu ET (2000) Identification of c-myc responsive genes using rat cDNA microarray. Cancer Res 60:5922–5928

    PubMed  CAS  Google Scholar 

  • Haggerty TJ, Zeller KI, Osthus RC, Wonsey DR, Dang CV (2003) A strategy for identifying transcription factor binding sites reveals two classes of genomic c-Myc target sites. Proc Natl Acad Sci U S A 100:5313–5318

    Article  PubMed  CAS  Google Scholar 

  • Huang E, Ishida S, Pittman J, Dressman H, Bild A, Kloos M, D’Amico M, Pestell RG, West M, Nevins JR (2003) Gene expression phenotypic models that predict the activity of oncogenic pathways. Nat Genet 18:18

    CAS  Google Scholar 

  • Hurlin PJ, Foley KP, Ayer DE, Eisenman RN, Hanahan D, Arbeit JM (1995a) Regulation of Myc and Mad during epidermal differentiation and HPV-associated tumorigenesis. Oncogene 11:2487–2501

    PubMed  CAS  Google Scholar 

  • Hurlin PJ, Quéva C, Koskinen PJ, Steingrimsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN (1995b) Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J 14:5646–5659

    PubMed  CAS  Google Scholar 

  • Iritani BM, Eisenman RN (1999) c-Myc enhances protein synthesis and cell size during B lymphocyte development. Proc Natl Acad Sci U S A 96:13180–13185

    Article  PubMed  CAS  Google Scholar 

  • Iritani BM, Delrow J, Grandori C, Gomez I, Klacking M, Carlos LS, Eisenman RN (2002) Modulation of T-lymphocyte development, growth and cell size by the Myc antagonist and transcriptional repressor Mad1. EMBO J 21:4820–4830

    Article  PubMed  CAS  Google Scholar 

  • James L, Eisenman RN (2002) Myc and Mad bHLHZ domains possess identical DNA-binding specificities but only partially overlapping functions in vivo. Proc Natl Acad Sci U S A 99:10429–10434

    Article  PubMed  CAS  Google Scholar 

  • Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P (1999) Drosophila myc regulates cellular growth during development. Cell 98:779–790

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Li Q, Dang CV, Lee LA (2000) Induction of ribosomal genes and hepatocyte hypertrophy by adenovirus-mediated expression of c-Myc in vivo. Proc Natl Acad Sci U S A 97:11198–11202

    Article  PubMed  CAS  Google Scholar 

  • Kim SY, Herbst A, Tworkowski KA, Salghetti SE, Tansey WP (2003) Skp2 regulates myc protein stability and activity. Mol Cell 11:1177–1188

    Article  PubMed  CAS  Google Scholar 

  • Larsson LG, Pettersson M, Oberg F, Nilsson K, Luscher B (1994) Expression of mad, mxi1, max and c-myc during induced differentiation of hematopoietic cells: opposite regulation of mad and c-myc. Oncogene 9:1247–1252

    PubMed  CAS  Google Scholar 

  • Lee TC, Li L, Philipson L, Ziff EB (1997) Myc represses transcription of the growth arrest gene gas1. Proc Natl Acad Sci U S A 94:12886–12891

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B (2003) Aglobal transcriptional regulatory role for c-Myc in Burkitt’s lymphoma cells. Proc Natl Acad Sci U S A 100:8164–8169

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Keefer JR, Wang QF, Friedman AD (2003) Reciprocal effects of C/EBPalpha and PKCdelta on JunB expression and monocytic differentiation depend upon the C/EBPalpha basic region. Blood 101:3885–3892

    Article  PubMed  CAS  Google Scholar 

  • Lossos IS, Alizadeh AA, Diehn M, Warnke R, Thorstenson Y, Oefner PJ, Brown PO, Botstein D, Levy R (2002) Transformation of follicular lymphoma to diffuse large-cell lymphoma: alternative patterns with increased or decreased expression of c-myc and its regulated genes. Proc Natl Acad Sci U S A 99:8886–8891

    Article  PubMed  CAS  Google Scholar 

  • Mao DY, Watson JD, Yan PS, Barsyte-Lovejoy D, Khosravi F, Wong WW, Farnham PJ, Huang TH, Penn LZ (2003) Analysis of Myc bound loci identified by CpG island arrays shows that Max is essential for Myc-dependent repression. Curr Biol 13:882–886

    Article  PubMed  CAS  Google Scholar 

  • Marhin WW, Chen S, Facchini LM, Fornace AJ Jr, Penn LZ (1997) Myc represses the growth arrest gene gadd45. Oncogene 14:2825–2834

    Article  PubMed  CAS  Google Scholar 

  • Mateyak MK, Obaya AJ, Adachi S, Sedivy JM (1997) Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination. Cell Growth Differ 8:1039–1048

    PubMed  CAS  Google Scholar 

  • Menssen A, Hermeking H (2002) Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Proc Natl Acad Sci U S A 99:6274–6279

    Article  PubMed  CAS  Google Scholar 

  • Miltenberger RJ, Sukow KA, Farnham PJ (1995) An E-box-mediated increase in cad transcription at the G1/S-phase boundary is suppressed by inhibitory c-Myc mutants. Mol Cell Biol 15:2527–2535

    PubMed  CAS  Google Scholar 

  • Morrish F, Giedt C, Hockenbery D (2003) c-MYC apoptotic function is mediated by NRF-1 target genes. Genes Dev 17:240–255

    Article  PubMed  CAS  Google Scholar 

  • Nair SK, Burley SK (2003) X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell 112:193–205

    Article  PubMed  CAS  Google Scholar 

  • Nikiforov MA, Chandriani S, O’Connell B, Petrenko O, Kotenko I, Beavis A, Sedivy JM, Cole MD (2002) A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism. Mol Cell Biol 22:5793–5800

    Article  PubMed  CAS  Google Scholar 

  • Nikiforov MA, Popov N, Kotenko I, Henriksson M, Cole MD (2003) The Mad and Myc basic domains are functionally equivalent. J Biol Chem 278:11094–11099

    Article  PubMed  CAS  Google Scholar 

  • O’Connell BC, Cheung AF, Simkevich CP, Tam W, Ren X, Mateyak MK, Sedivy JM (2003) A large scale genetic analysis of c-Myc-regulated gene expression patterns. J Biol Chem 278:12563–12573

    Article  PubMed  CAS  Google Scholar 

  • O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843

    Article  PubMed  CAS  Google Scholar 

  • O’Hagan RC, Schreiber-Agus N, Chen K, David G, Engelman JA, Schwab R, Alland L, Thomson C, Ronning DR, Sacchettini JC, et al (2000) Gene-target recognition among members of the myc superfamily and implications for oncogenesis. Nat Genet 24:113–119

    Article  PubMed  CAS  Google Scholar 

  • Orian A, Van Steensel B, Delrow J, Bussemaker HJ, Li L, Sawado T, Williams E, Loo LW, Cowley SM, Yost C, et al (2003) Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network. Genes Dev 17:1101–1114

    Article  PubMed  CAS  Google Scholar 

  • Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA, Dang CV (2000) Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem 275:21797–21800

    Article  PubMed  CAS  Google Scholar 

  • Quéva C, McArthur GA, Iritani BM, Eisenman RN (2001) Targeted deletion of the S-phase specific Myc antagonist Mad3 sensitizes neural and lymphoid cells to radiation-induced apoptosis. Mol Cell Biol 21:703–712

    Article  PubMed  Google Scholar 

  • Roussel MF, Ashmun RA, Sherr CJ, Eisenman RN, Ayer DE (1996) Inhibition of cell proliferation by the Mad1 transcriptional repressor. Mol Cell Biol 16:2796–2801

    PubMed  CAS  Google Scholar 

  • Schreiber-Agus N, Chin L, Chen K, Torres R, Rao G, Guida P, Skoultchi I, DePinho RA (1995) An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast repressor SIN3. Cell 80:777–786

    Article  PubMed  CAS  Google Scholar 

  • Schuldiner O, Benvenisty NA (2001) DNA microarray screen for genes involved in c-MYC and N-MYC oncogenesis in human tumors. Oncogene 20:4984–4994

    Article  PubMed  CAS  Google Scholar 

  • Seoane J, Le HV, Massague J (2002) Myc suppression of the p21(Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature 419:729–734

    Article  PubMed  CAS  Google Scholar 

  • Shiio Y, Donohoe S, Yi EC, Goodlett DR, Aebersold R, Eisenman RN (2002) Quantitative proteomic analysis of Myc oncoprotein function. EMBO J 21:5088–5096

    Article  PubMed  CAS  Google Scholar 

  • Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Moroy T, Bartek J, Massague J, Hanel F, Eilers M (2001) Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol 3:392–399

    Article  PubMed  CAS  Google Scholar 

  • von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C, Hydbring P, Weidung I, Nakayama K, Nakayama KI, et al (2003) The F-box protein Skp2 participates in c-Myc proteasomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell 11:1189–1200

    Article  PubMed  Google Scholar 

  • Watson JD, Oster SK, Shago M, Khosravi F, Penn LZ (2002) Identifying genes regulated in a Myc-dependent manner. J Biol Chem 277:36921–36930

    Article  PubMed  CAS  Google Scholar 

  • Wechsler DS, Shelly CA, Petroff CA, Dang CV(1997) MXI1, a putative tumor suppressor gene, suppresses growth of human glioblastoma cells. Cancer Res 57:4905–4912

    PubMed  CAS  Google Scholar 

  • Wonsey DR, Zeller KI, Dang CV (2002) The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc Natl Acad Sci U S A 99:6649–6654

    Article  PubMed  CAS  Google Scholar 

  • Wu KJ, Polack A, Dalla-Favera R (1999) Coordinated regulation of iron-controlling genes, H-ferritin and IRP2, by c-MYC. Science 283:676–679

    Article  PubMed  CAS  Google Scholar 

  • Wu S, Cetinkaya C, Munoz-Alonso MJ, von der Lehr N, Bahram F, Beuger V, Eilers M, Leon J, Larsson LG (2003) Myc represses differentiation-induced p21CIP1 expression via Miz-1-dependent interaction with the p21 core promoter. Oncogene 22:351–360

    Article  PubMed  CAS  Google Scholar 

  • Yang BS, Geddes TJ, Pogulis RJ, de Crombrugghe B, Freytag SO (1991) Transcriptional suppression of cellular gene expression by c-Myc. Mol Cell Biol 11:2291–2295

    PubMed  CAS  Google Scholar 

  • Yin XY, Grove LE, Prochownik EV (2001) Mmip-2/Rnf-17 enhances c-Myc functionand regulates some target genes in common with glucocorticoid hormones. Oncogene 20:2908–2917

    Article  PubMed  CAS  Google Scholar 

  • Zeller KI, Haggerty TJ, Barrett JF, Guo Q, Wonsey DR, Dang CV (2001) Characterization of nucleophosmin (B23) as a Myc target by scanning chromatin immunoprecipitation. J Biol Chem 276:48285–48291

    PubMed  CAS  Google Scholar 

  • Zervos AS, Gyuris J, Brent R (1993) Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72:223–232

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, The Johns Hopkins University School of Medicine, Ross 1032, 720 Rutland Avenue, Baltimore, MD, 21205, USA

    L. A. Lee & C. V. Dang

Authors
  1. L. A. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. V. Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. V. Dang .

Editor information

Editors and Affiliations

  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Seattle, Washington, 98108-1024, USA

    R. N. Eisenman Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Lee, L.A., Dang, C.V. (2006). Myc Target Transcriptomes. In: Eisenman, R.N. (eds) The Myc/Max/Mad Transcription Factor Network. Current Topics in Microbiology and Immunology, vol 302. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-32952-8_6

Download citation

Publish with us

Policies and ethics

Search

Navigation