Requirements for Cell Cycle Arrest by p16INK4a
| Autor: | Jacqueline L. Bruce, Marie Classon, Robert Hurford, Nicholas J. Dyson, James Koh |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cell cycle checkpoint
Blotting Western Cyclin A Repressor Retinoblastoma-Like Protein p107 Biology Retinoblastoma Protein S Phase Mice Fetus Cyclin D1 Proto-Oncogene Proteins Animals E2F neoplasms Molecular Biology Cells Cultured Cyclin-Dependent Kinase Inhibitor p16 Cyclin Mice Knockout Retinoblastoma-Like Protein p130 Kinase G1 Phase Retinoblastoma protein Cyclin-Dependent Kinase 4 Nuclear Proteins Proteins Cell Biology Fibroblasts Phosphoproteins Cyclin-Dependent Kinases Cell biology Gene Expression Regulation Neoplastic embryonic structures biology.protein biological phenomena cell phenomena and immunity Carrier Proteins |
| Zdroj: | Molecular Cell. 6:737-742 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(00)00072-1 |
| Popis: | Analysis of tumor-derived mutations has led to the suggestion that p16 INK4a , cyclin D1, cdk4, and the retinoblastoma protein (pRB) are components of a regulatory pathway that is inactivated in most tumor cells. Cell cycle arrest induced by p16 INK4a , an inhibitor of cyclin D–dependent kinases, requires pRB, and it has been proposed that this G1 arrest is mediated by pRB–E2F repressor complexes. By comparing the properties of primary mouse embryonic fibroblasts specifically lacking pRB-family members, we find that pRB is insufficient for a p16 INK4a -induced arrest. In addition to pRB, a second function provided by either p107 or p130, two pRB-related proteins, is required for p16 INK4a to block DNA synthesis. We infer that p16 INK4a -induced arrest is not mediated exclusively by pRB, but depends on the nonredundant functions of at least two pRB-family members. |
| Databáze: | OpenAIRE |
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