Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner.
Cyclin E is classified as a putative G1 cyclin on the basis of its cyclic pattern of mRNA expression, with maximal levels being detected near the G1/S boundary. We report here that cyclin E is found associated with the transcription factor E2F in a temporally regulated fashion. E2F is known to be a critical transcription factor for the expression of some S phase-specific proteins and is thought to be important for a series of others. Antisera specific for cyclin E were raised and used to demonstrate an association between cyclin E and E2F. This cyclin E/E2F complex was seen in a variety of human cell lines from various tissues, but its appearance was detected primarily during the G1 phase of the cell cycle. The cyclin E/E2F association decreased as cells entered S phase, just as the association of E2F with cyclin A became detectable. We characterized the cyclin E-E2F complex further to show that both the cyclin-dependent kinase-2 (cdk2) and p107 were present. Therefore, the p107/E2F complex is associated with two different cdk2 kinase complexes--one containing cyclin A and the other containing cyclin E--and the appearance of these complexes is temporally regulated during the cell cycle. The presence of cyclin E/E2F complexes in the G1 phase suggests a role for cyclin E in the control of genes required for the G1-to-S transition.
Lees
E
E
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Faha
B
B
Dulic
V
V
Reed
S I
SI
Harlow
E
E
D001483:Base Sequence; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004591:Electrophoresis, Polyacrylamide Gel; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D007106:Immune Sera; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009841:Oligonucleotides; D011233:Precipitin Tests; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D007106:Immune Sera; D009687:Nuclear Proteins; D009841:Oligonucleotides; D011506:Proteins; C493844:RBL1 protein, human; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050680:Transcription Factor DP1; D014157:Transcription Factors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases