Early phosphorylation of the retinoblastoma gene product regulates protein binding to the c-fos retinoblastoma control element during T cell activation
| Autor: | Stephen H. Benedict, Michael Branden, Lisa K. Felzien |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
T-Lymphocytes Immunology Regulatory Sequences Nucleic Acid Biology Lymphocyte Activation Resting Phase Cell Cycle Retinoblastoma Protein S Phase Dephosphorylation Jurkat Cells chemistry.chemical_compound Okadaic Acid medicine Humans Phosphorylation E2F neoplasms Molecular Biology Ionophores Retinoblastoma G1 Phase Genes fos DNA Protein phosphatase 2 Okadaic acid Cell cycle medicine.disease Molecular biology DNA-Binding Proteins Gene Expression Regulation chemistry biological phenomena cell phenomena and immunity Cell activation Protein Binding Transcription Factors |
| Zdroj: | Molecular Immunology. 34:507-517 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/s0161-5890(97)00063-1 |
| Popis: | Function of the retinoblastoma tumor suppressor protein [pRb] is regulated by phosphorylation during the G1 and S phases of the cell cycle. pRb regulates transcription of several genes, including c-fos. However, since c-fos is regulated during exit from G0, it has remained unclear how pRb participates in c-fos regulation. We have identified a protein complex, the retinoblastoma control factor A [RCF-A] which binds to the c-fos retinoblastoma control element [RCE] and is regulated by pRb within 10 min after T cell activation. We demonstrate that pRb control of RCF-A is dependent upon the state of phosphorylation of pRb. pRb becomes hyperphosphorylated on specific peptides at 10 min after mitogenic stimulation and pRb is dephosphorylated by 30 min. This time course coincides with RCF-A DNA binding. RCF-A binds RCE DNA longer when cells are treated with okadaic acid, and okadaic acid prevents pRb dephosphorylation. Dephosphorylated pRb inhibits RCF-A binding in vitro but phosphorylated pRb does not. Thus, in addition to the described G1/S regulation of pRb, transient inactivation by phosphorylation of pRb in T cells may also be important as resting cells leave G0. |
| Databáze: | OpenAIRE |
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