C/EBPα Arrests Cell Proliferation through Direct Inhibition of Cdk2 and Cdk4
| Autor: | Nikolai A. Timchenko, Margie Wilde, Triona Goode, Hongmei Wang, William J. Roesler, Alana L. Welm, Polina Iakova |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Recombinant Fusion Proteins
Molecular Sequence Data Protein Serine-Threonine Kinases Biology Cell Fractionation Protein Structure Secondary Cell Line Mice Genes Reporter Proto-Oncogene Proteins Enhancer binding CCAAT-Enhancer-Binding Protein-alpha CDC2-CDC28 Kinases Animals Amino Acid Sequence Enzyme Inhibitors Molecular Biology Transcription factor Cyclin Mice Knockout Ccaat-enhancer-binding proteins Cell growth Kinase Cyclin-Dependent Kinase 2 Cyclin-dependent kinase 2 Cyclin-Dependent Kinase 4 Nuclear Proteins Cell Biology Molecular biology Cyclin-Dependent Kinases Rats Cell biology Liver Cell culture biology.protein biological phenomena cell phenomena and immunity Cell Division |
| Zdroj: | Molecular Cell. 8:817-828 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/s1097-2765(01)00366-5 |
| Popis: | The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a strong inhibitor of cell proliferation. We found that C/EBPalpha directly interacts with cdk2 and cdk4 and arrests cell proliferation by inhibiting these kinases. We mapped a short growth inhibitory region of C/EBPalpha between amino acids 175 and 187. This portion of C/EBPalpha is responsible for direct inhibition of cyclin-dependent kinases and causes growth arrest in cultured cells. C/EBPalpha inhibits cdk2 activity by blocking the association of cdk2 with cyclins. Importantly, the activities of cdk4 and cdk2 are increased in C/EBPalpha knockout livers, leading to increased proliferation. Our data demonstrate that the liver-specific transcription factor C/EBPalpha brings about growth arrest through direct inhibition of cdk2 and cdk4. |
| Databáze: | OpenAIRE |
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