Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1993 Apr 15; 90(8): 3685–3689.
PMCID: PMC46366

Differential modulation of cyclin gene expression by MYC.

Abstract

We have investigated the effects of deregulated expression of the human c-MYC protooncogene on cyclin gene expression and on the transcription factor E2F. We found that constitutive expression of MYC or activation of conditional MycER chimeras led to higher levels of cyclin A and cyclin E mRNA. Activation of cyclin A expression by MYC led to a growth factor-independent association of cyclin A and cdk2 with the transcription factor E2F and correlated with an increase in E2F transcriptional activity. In contrast, expression of the G1 phase cyclin D1 was strongly reduced in MYC-transformed cells. In synchronized cells, repression of cyclin D1 by MYC occurred very early in the G1 phase of the cell cycle.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Lüscher B, Christenson E, Litchfield DW, Krebs EG, Eisenman RN. Myb DNA binding inhibited by phosphorylation at a site deleted during oncogenic activation. Nature. 1990 Apr 5;344(6266):517–522. [PubMed]
  • Lüscher B, Eisenman RN. c-myc and c-myb protein degradation: effect of metabolic inhibitors and heat shock. Mol Cell Biol. 1988 Jun;8(6):2504–2512. [PMC free article] [PubMed]
  • Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. Sequence-specific DNA binding by the c-Myc protein. Science. 1990 Nov 23;250(4984):1149–1151. [PubMed]
  • Prendergast GC, Ziff EB. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science. 1991 Jan 11;251(4990):186–189. [PubMed]
  • Prendergast GC, Lawe D, Ziff EB. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell. 1991 May 3;65(3):395–407. [PubMed]
  • Blackwood EM, Eisenman RN. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. [PubMed]
  • Amati B, Dalton S, Brooks MW, Littlewood TD, Evan GI, Land H. Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. Nature. 1992 Oct 1;359(6394):423–426. [PubMed]
  • Kretzner L, Blackwood EM, Eisenman RN. Myc and Max proteins possess distinct transcriptional activities. Nature. 1992 Oct 1;359(6394):426–429. [PubMed]
  • Mugrauer G, Ekblom P. Contrasting expression patterns of three members of the myc family of protooncogenes in the developing and adult mouse kidney. J Cell Biol. 1991 Jan;112(1):13–25. [PMC free article] [PubMed]
  • Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ, Hancock DC. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. [PubMed]
  • Eilers M, Schirm S, Bishop JM. The MYC protein activates transcription of the alpha-prothymosin gene. EMBO J. 1991 Jan;10(1):133–141. [PMC free article] [PubMed]
  • Kirschner M. The cell cycle then and now. Trends Biochem Sci. 1992 Aug;17(8):281–285. [PubMed]
  • Land H, Parada LF, Weinberg RA. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. [PubMed]
  • Figge J, Webster T, Smith TF, Paucha E. Prediction of similar transforming regions in simian virus 40 large T, adenovirus E1A, and myc oncoproteins. J Virol. 1988 May;62(5):1814–1818. [PMC free article] [PubMed]
  • Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M, Weinberg RA, Harlow E. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature. 1988 Jul 14;334(6178):124–129. [PubMed]
  • Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR. The E2F transcription factor is a cellular target for the RB protein. Cell. 1991 Jun 14;65(6):1053–1061. [PubMed]
  • Bandara LR, La Thangue NB. Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. Nature. 1991 Jun 6;351(6326):494–497. [PubMed]
  • Rustgi AK, Dyson N, Bernards R. Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product. Nature. 1991 Aug 8;352(6335):541–544. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Eilers M, Picard D, Yamamoto KR, Bishop JM. Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells. Nature. 1989 Jul 6;340(6228):66–68. [PubMed]
  • Fort P, Marty L, Piechaczyk M, el Sabrouty S, Dani C, Jeanteur P, Blanchard JM. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. [PMC free article] [PubMed]
  • Pines J, Hunter T. Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B. Nature. 1990 Aug 23;346(6286):760–763. [PubMed]
  • Matsushime H, Roussel MF, Ashmun RA, Sherr CJ. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991 May 17;65(4):701–713. [PubMed]
  • Boeuf H, Jansen-Durr P, Kédinger C. EIa-mediated transactivation of the adenovirus EIIa early promoter is restricted in undifferentiated F9 cells. Oncogene. 1990 May;5(5):691–699. [PubMed]
  • Pagano M, Draetta G, Jansen-Dürr P. Association of cdk2 kinase with the transcription factor E2F during S phase. Science. 1992 Feb 28;255(5048):1144–1147. [PubMed]
  • Jansen-Durr P, Boeuf H, Kédinger C. Cooperative binding of two E2F molecules to an Ela-responsive promoter is triggered by the adenovirus Ela, but not by a cellular Ela-like activity. EMBO J. 1989 Nov;8(11):3365–3370. [PMC free article] [PubMed]
  • Mudryj M, Devoto SH, Hiebert SW, Hunter T, Pines J, Nevins JR. Cell cycle regulation of the E2F transcription factor involves an interaction with cyclin A. Cell. 1991 Jun 28;65(7):1243–1253. [PubMed]
  • Bagchi S, Weinmann R, Raychaudhuri P. The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F. Cell. 1991 Jun 14;65(6):1063–1072. [PubMed]
  • Hiebert SW, Chellappan SP, Horowitz JM, Nevins JR. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 1992 Feb;6(2):177–185. [PubMed]
  • Shirodkar S, Ewen M, DeCaprio JA, Morgan J, Livingston DM, Chittenden T. The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner. Cell. 1992 Jan 10;68(1):157–166. [PubMed]
  • Ewen ME, Xing YG, Lawrence JB, Livingston DM. Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell. 1991 Sep 20;66(6):1155–1164. [PubMed]
  • Pagano M, Dürst M, Joswig S, Draetta G, Jansen-Dürr P. Binding of the human E2F transcription factor to the retinoblastoma protein but not to cyclin A is abolished in HPV-16-immortalized cells. Oncogene. 1992 Sep;7(9):1681–1686. [PubMed]
  • Karn J, Watson JV, Lowe AD, Green SM, Vedeckis W. Regulation of cell cycle duration by c-myc levels. Oncogene. 1989 Jun;4(6):773–787. [PubMed]
  • Royer-Pokora B, Beug H, Claviez M, Winkhardt HJ, Friis RR, Graf T. Transformation parameters in chicken fibroblasts transformed by AEV and MC29 avian leukemia viruses. Cell. 1978 Apr;13(4):751–760. [PubMed]
  • Pagano M, Pepperkok R, Verde F, Ansorge W, Draetta G. Cyclin A is required at two points in the human cell cycle. EMBO J. 1992 Mar;11(3):961–971. [PMC free article] [PubMed]
  • Yang BS, Geddes TJ, Pogulis RJ, de Crombrugghe B, Freytag SO. Transcriptional suppression of cellular gene expression by c-Myc. Mol Cell Biol. 1991 Apr;11(4):2291–2295. [PMC free article] [PubMed]
  • Suen TC, Hung MC. c-myc reverses neu-induced transformed morphology by transcriptional repression. Mol Cell Biol. 1991 Jan;11(1):354–362. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...