The adenoviral E1A oncoproteins interfere with the growth-inhibiting effect of the cdk-inhibitor p21(CIP1/WAF1)
| Autor: | A. F. A. S. Teunisse, A. J. Van Der Eb, Josephine C. Dorsman, P. Keblusek, H. Teunissen, A. Zantema |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Recombinant Fusion Proteins Gene Expression Biology Transfection Cell Line chemistry.chemical_compound Cyclins Virology Animals Humans Enzyme Inhibitors neoplasms Cyclin Kinase Cell growth Adenoviruses Human G1 Phase DNA replication Cell Transformation Viral Cyclin-Dependent Kinases Rats Proliferating cell nuclear antigen chemistry Cancer research biology.protein Adenovirus E1A Proteins biological phenomena cell phenomena and immunity Growth inhibition Cell Division Function (biology) CDK inhibitor |
| Zdroj: | Journal of General Virology. 80:381-390 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/0022-1317-80-2-381 |
| Popis: | The cdk-inhibitor p21(CIP1/WAF1) inhibits the activities of cyclin-dependent kinases and proliferating cell nuclear antigen, thereby repressing cell-cycle progression and DNA replication. Transforming oncogenes, such as E1A of human adenovirus 5 (Ad5), may interfere with such growth-inhibitory proteins. In this study, we show that in various Ad5E1-transformed cells, p21(CIP1/WAF1) is expressed and that, in general, expression is not downregulated. In addition, colony-formation assays show that in Ad5E1-transformed cells highly overexpressed p21(CIP1/WAF1) can still cause growth inhibition. FACS experiments indicate, however, that a G1 arrest induced by moderate overexpression of p21(CIP1/WAF1) can be overcome by E1A. The E1A proteins may interfere with the function of p21(CIP1/WAF1) by binding. Indeed, p21(CIP1/WAF1) binds with its cyclin/cdk-binding N terminus to the transforming N-terminal and CR1 region of the E1A proteins. Together, these results lend support to the model that E1A can interfere directly with p21(CIP1/WAF1) function and thereby stimulates cell growth. |
| Databáze: | OpenAIRE |
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