title: Differential control of transcription by DNA-bound cyclins.
abstract: Different cyclins mediate different cell-cycle transitions. Some cyclins, such as cyclin A and cyclin E, form stable complexes with proteins that bind directly or indirectly to DNA and thus might be recruited to certain regions of the genome at specific times in the cell cycle. Furthermore, cyclins contain structural motifs that are also present in known transcriptional modulators. We found that cyclin A is a potent transcriptional repressor and cyclin E is a potent transcriptional activator when bound to DNA via a heterologous DNA binding domain. The former activity was linked to the integrity of the cyclin A cyclin fold, whereas the latter activity related to the ability of cyclin E to activate cdk2 and recognize substrates. Furthermore, we found that cyclin E, but not cyclin A, activated transcription in a cell-cycle-dependent manner when present in physiological concentrations as an unfused protein. These results suggest that cyclin A and cyclin E intrinsically differ with respect to their ability to modulate transcription when tethered to DNA.
authors.affiliation: Brigham and Womens Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: T Y
authors.initials: TY
authors.lastname: Kim
authors.forename: W G
authors.initials: WG
authors.lastname: Kaelin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D042846:CDC2-CDC28 Kinases; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D019925:Cyclin A; D019927:Cyclin E; D012097:Repressor Proteins; D015534:Trans-Activators; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D004318:Doxycycline