Functional Inactivation of the Retinoblastoma Protein Requires Sequential Modification by at Least Two Distinct Cyclin-cdk Complexes
| Autor: | Ante S. Lundberg, Robert A. Weinberg |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Cyclin A
Cell Cycle Proteins macromolecular substances Protein Serine-Threonine Kinases Transfection Retinoblastoma Protein environment and public health Cyclin-dependent kinase Cyclin D Cyclins Proto-Oncogene Proteins Cyclin E CDC2-CDC28 Kinases Humans Phosphorylation E2F Cell Growth and Development neoplasms Molecular Biology Cells Cultured Cyclin Cell Nucleus biology Kinase Cyclin-Dependent Kinase 2 Cyclin-dependent kinase 2 G1 Phase Retinoblastoma protein Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 Cell Biology Molecular biology Cyclin-Dependent Kinases E2F Transcription Factors Cell biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) biology.protein biological phenomena cell phenomena and immunity Carrier Proteins Transcription Factor DP1 Cyclin A2 Retinoblastoma-Binding Protein 1 Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 18:753-761 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.18.2.753 |
| Popis: | The retinoblastoma protein (pRb) acts to constrain the G1-S transition in mammalian cells. Phosphorylation of pRb in G1 inactivates its growth-inhibitory function, allowing for cell cycle progression. Although several cyclins and associated cyclin-dependent kinases (cdks) have been implicated in pRb phosphorylation, the precise mechanism by which pRb is phosphorylated in vivo remains unclear. By inhibiting selectively either cdk4/6 or cdk2, we show that endogenous D-type cyclins, acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Furthermore, cyclin E-cdk2 is unable to phosphorylate pRb in the absence of prior phosphorylation by cyclin D-cdk4/6 complexes. Complete phosphorylation of pRb, inactivation of E2F binding, and activation of E2F transcription occur only after sequential action of at least two distinct G1 cyclin kinase complexes. |
| Databáze: | OpenAIRE |
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