The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
FKBP-rapamycin inhibits a cyclin-dependent kinase activity and a cyclin D1-Cdk association in early G1 of an osteosarcoma cell line
Open accessAbstract
Upon entering a cell the natural product rapamycin, like the structurally related immunosuppressant FK506, associates with members of the FKBP family of proteins. One or more of the resulting FKBP-rapamycin complexes blocks signaling pathways emanating from some growth factor receptors. Recently, the addition of rapamycin was shown to inhibit the phosphorylation and activation of a 70-kDa ribosomal S6 protein kinase, which normally occurs minutes after the activation of certain cytokine and growth factor receptors. We now report that rapamycin can be added 4 to 6 h after the addition of serum growth factors to quiescent human osteosarcoma cells and still arrest these cells in G1. This window of action correlates with the inducible appearance of a cyclin-dependent kinase (cdk) activity, and the induction of this activity is inhibited by the addition of rapamycin. Furthermore, p36cyclin D1 associates with this cdk protein complex in lysates of untreated cells, but does not associate with this cdk protein complex in lysates of rapamycin-treated cells. Together, these studies demonstrate that FKBP-rapamycin can modulate a cyclin-dependent kinase activity and a cyclin D1-cdk association during early G1 in MG-63 human osteosarcoma cells.
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From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [218]
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Metadata
- Authors
- Albers, M. W., Williams, R. T., Brown, E. J., Tanaka, A., Hall, F. L., & Schreiber, S. L.
- Affiliations
- Harvard University (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1993-10
- Volume
- 268
- Issue
- 30
- Pages
- 22825-22829
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1485463834
- Cited by
- 145
- References
- 26
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2015: 5 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM38627)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- rapamycin, cyclin-dependent kinases, cyclin D1, G1 cell cycle arrest, osteosarcoma, MG-63 cells, cell cycle regulation, FK506
- MeSH terms
- Carrier Proteins, Heat-Shock Proteins, Protamine Kinase, Humans, Immunosuppressive Agents, Polyenes, Protein Binding, Osteosarcoma, Tumor Cells, Cultured, G1 Phase, S Phase, Cyclins, Protein Serine-Threonine Kinases, Cyclin-Dependent Kinases, Sirolimus, Tacrolimus Binding Proteins, CDC2-CDC28 Kinases, Protein Kinase Inhibitors, Cyclin-Dependent Kinase 2
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