Thymidine kinase transcription is regulated at G1/S phase by a complex that contains retinoblastoma-like protein and a cdc2 kinase.
Transcription of the murine thymidine kinase gene, which is coregulated with the G1/S phase transition, is activated by changing the binding of protein complexes Yi1 and Yi2 to three upstream DNA motifs. Yi1 is replaced by Yi2 shortly before S phase. Yi1 contains a protein of 110 kDa that binds to the DNA motif sites and may be an underphosphorylated murine retinoblastoma protein, shown by its molecular mass, timing of its activity, and antibody recognition. An H1 kinase related to cdc2 cofractionates with both complexes. We propose that this kinase phosphorylates the murine retinoblastoma protein, releasing transcriptional inhibitions by Yi1 and permitting cell cycle progression. These results provide a cycle-related molecular target for such complexes. They are based on investigations of cycle control in uninfected cells. The Yi complexes are similar but not identical to complexes that include a cellular protein, E2F, that was originally found to bind to adenovirus DNA.
Dou
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Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, MA 02115.
Markell
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PJ
Pardee
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D000818:Animals; D016203:CDC2 Protein Kinase / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015151:Immunoblotting; D046911:Macromolecular Substances; D051379:Mice; D009838:Oligodeoxyribonucleotides; D016160:Retinoblastoma Protein / Q000302:isolation & purification / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D016160:Retinoblastoma Protein; D013937:Thymidine Kinase; D016203:CDC2 Protein Kinase