Cited by 146PI3K/AKT/mTOR signaling in cancerCancer-related Molecular PathwaysSignaling Pathways in Disease

FKBP-rapamycin inhibits a cyclin-dependent kinase activity and a cyclin D1-Cdk association in early G1 of an osteosarcoma cell line

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Albers, M.W., Williams, R.T., Brown, E.J., Tanaka, A, Hall, F.L., Schreiber, S.L.·1993·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1016/s0021-9258(18)41602-x

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  • Anthracyclines exert antitumor activity mainly by inhibiting topoisomerase II.

    “Anthracyclines are among the most widely used antitumor antibiotics in the clinic and exert antitumor activity mainly by inhibiting topoisomerase II [215,216,217,218,219].”

    From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [218]

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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
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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