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Cited by 342

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 access
Hashemolhosseini, Said, Nagamine, Yoshikuni, Morley, Simon J., Desrivières, Sylvane, Mercep, Luka, Ferrari, Stefano·1998·Journal of Biological Chemistry

Abstract

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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CoChat. (2026). Citation check: Rapamycin Inhibition of the G1 to S Transition Is Mediated by Effects on Cyclin D1 mRNA and Protein Stability. https://app.cochat.ai/papers/10.1074/jbc.273.23.14424
The paper
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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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.