The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Rapamycin Inhibition of the G1 to S Transition Is Mediated by Effects on Cyclin D1 mRNA and Protein Stability
Open accessAbstract
The immunosuppressant rapamycin has been shown previously to inhibit the G1/S transition in several cell types by prolonging the G1 phase of the cell cycle. This process appears to be controlled, in part, by the rapamycin-sensitive FK506-binding protein-rapamycin-associated protein-p70 S6 kinase (p70(S6k)) pathway and the cyclin-dependent kinases (Cdk). We now show that in serum-stimulated NIH 3T3 cells, rapamycin treatment delays the accumulation of cyclin D1 mRNA during progression through G1. Rapamycin also appears to affect stability of the transcript. The combined transcriptional and post-transcriptional effects of the drug ultimately result in decreased levels of cyclin D1 protein. Moreover, degradation of newly synthesized cyclin D1 protein is accelerated by rapamycin, a process prevented by inclusion of the proteasome inhibitor, N-acetyl-Leu-Leu-norleucinal. The overall effect of rapamycin on cyclin D1 leads, in turn, to impaired formation of active complexes with Cdk4, a process which triggers retargeting of the p27(Kip1) inhibitor to cyclin E/Cdk2. In view of this novel experimental evidence, we discuss a possible mechanism for the rapamycin-induced cell cycle arrest at the G1/S transition.
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Metadata
- Authors
- Hashemolhosseini, S., Nagamine, Y., Morley, S. J., Desrivières, S., Mercep, L., & Ferrari, S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 273
- Issue
- 23
- Pages
- 14424-14429
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2006874274
- Cited by
- 342
- References
- 64
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Hashemolhosseini, S., Nagamine, Y., Morley, S. J., Desrivières, S., Mercep, L., & Ferrari, S. (1998). Rapamycin Inhibition of the G1 to S Transition Is Mediated by Effects on Cyclin D1 mRNA and Protein Stability. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.23.14424
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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