Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events.
The c-myc gene has been implicated in three distinct genetic programs regulating cell proliferation: control of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth. We have now used p27(-/-) fibroblasts to dissect these downstream signalling pathways. In these cells, activation of Myc stimulates transcription of E2F target genes, S-phase entry and cell growth without affecting cyclin E-cdk2 kinase activity. Both cyclin D2 and E2F2, potential direct target genes of Myc, are induced in p27(-/-) MycER cells. Ectopic expression of E2F2, but not of cyclin D2, induces S-phase entry, but, in contrast to Myc, does not stimulate cell growth. Our results show that stimulation of cyclin E-cdk2 kinase, of E2F-dependent transcription and of cell growth by Myc can be genetically separated from each other.
Beier
R
R
Institute of Molecular Biology and Tumour Research, Emil-Mannkopff-Strabetae 2, 35033 Marburg, Germany.
Bürgin
A
A
Kiermaier
A
A
Fero
M
M
Karsunky
H
H
Saffrich
R
R
Möröy
T
T
Ansorge
W
W
Roberts
J
J
Eilers
M
M
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division; D002478:Cells, Cultured; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004790:Enzyme Induction; D016259:Genes, myc; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D056465:Retinoblastoma-Binding Protein 1; D012190:Retroviridae / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008869:Microtubule-Associated Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases