Differential modulation of cyclin gene expression by MYC.
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.
Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschüngs Zentrüm, Heidelberg, Federal Republic of Germany.
P
P
Jansen-Dürr
A
A
Meichle
P
P
Steiner
M
M
Pagano
K
K
Finke
J
J
Botz
J
J
Wessbecher
G
G
Draetta
M
M
Eilers
D016475:3T3 Cells; D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D016213:Cyclins / Q000235:genetics*; D015342:DNA Probes; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004967:Estrogens / Q000494:pharmacology; D016193:G1 Phase; D015870:Gene Expression; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D016259:Genes, myc; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D009053:Sarcoma Viruses, Murine / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004967:Estrogens; D011993:Recombinant Fusion Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D001616:beta-Galactosidase; D015739:Nocodazole