The Rb-related p107 protein can suppress E2F function independently of binding to cyclin A/cdk2.
The interaction of the retinoblastoma susceptibility gene product (Rb)-related p107 protein with the E2F transcription factor in S-phase cells facilitates the formation of a multicomponent complex also containing cyclin A and the p33cdk2 kinase. We have created a series of p107 mutants to assess the ability of p107 to inhibit E2F function and the role of the cyclin A/cdk2 complex in this process. We find that p107 mutants that do not bind to E2F also fail to repress E2F-dependent transcription. Moreover, we find that the ability of p107 to suppress E2F-dependent transcription is not dependent on the ability of p107 to associate with cyclin A/cdk2. Finally, an analysis of the ability of the p107 mutant proteins to suppress cell growth suggests that both E2F-dependent and E2F-independent events correlate with this activity.
Smith
E J
EJ
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Nevins
J R
JR
D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D009687:Nuclear Proteins; C493844:RBL1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D056465:Retinoblastoma-Binding Protein 1; D050720:Retinoblastoma-Like Protein p107; D050680:Transcription Factor DP1; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases