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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lee, A. S. Naeve, G. S. Li, L. J. |
| Description | Author Affiliation: Li LJ ( Department of Biochemistry, University of Southern California School of Medicine, Los Angeles 90033.); |
| Abstract | The cyclins are an extensive family of proteins whose cell cycle-dependent synthesis is postulated to control multiple events during the cell cycle. The synthesis of A-type cyclins begins at the start of S phase. In mammalian cells, association with the cdc-type kinases suggests that cyclin A complexes are important for DNA replication and regulating other DNA-bound substrates required for S phase. We report here that a 25-bp promoter element previously shown to be important for the G1-S activation of the human thymidine kinase (htk) promoter in growth-stimulated cells is a cellular target of cyclin A and the p33cdk2 complexes. Though the p33cdk2 and other nuclear factor complexes exhibit constitutive binding to the htk G1-S regulatory domain, the binding activity of a cyclin A/p107 protein complex is greatly enhanced when the cells enter S phase, correlating with the increase in the tk mRNA levels and the replication of DNA. The binding activity of the cyclin A complex is maintained throughout S phase. Mutation of the DNA sequences on either half of the 25-bp protein binding site results in the loss of its ability to compete efficiently in vitro for the htk complexes, including that of cyclin A-containing complex. The loss of high-affinity binding for the htk complexes also substantially reduces the S-phase regulation of the htk promoter in vivo. Our results support the hypothesis that a cyclin A complex, in association with the p33cdk2 kinase, mediates the S-phase-regulated transcription of the htk promoter in growth-stimulated cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 90 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1993-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CDC2-CDC28 Kinases Cell Cycle Genetics Cyclin-Dependent Kinases Cyclins Metabolism Gene Expression Regulation Promoter Regions, Genetic Protein Kinases Protein-Serine-Threonine Kinases Thymidine Kinase Transcription, Genetic Physiology Cell Line Chloramphenicol O-Acetyltransferase Cyclin-Dependent Kinase 2 DNA-Binding Proteins G1 Phase Kinetics Molecular Sequence Data Oligodeoxyribonucleotides Recombinant Fusion Proteins Regulatory Sequences, Nucleic Acid S Phase Time Factors Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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