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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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]
Cites
Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast
Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,010 · see citing works
Chung, J., Kuo, C. J., Crabtree, G. R., & Blenis, J. (1992) · Cell · doi:10.1016/0092-8674(92)90643-q · Cited by 1,151 · see citing works
Formation and Activation of a Cyclin E-cdk2 Complex During the G 1 Phase of the Human Cell Cycle
Koff, A., Giordano, A., Desai, D., Yamashita, K., Harper, J. W., Elledge, S. J., Nishimoto, T., Morgan, D. O., Franza, B. R., & Roberts, J. M. (1992) · Science · doi:10.1126/science.1388288 · Cited by 1,043 · see citing works
Xiong, Y., Zhang, H., & Beach, D. (1992) · Cell · doi:10.1016/0092-8674(92)90518-h · Cited by 1,021 · see citing works
Functional interactions of the retinoblastoma protein with mammalian D-type cyclins
Ewen, M. E., Sluss, H. K., Sherr, C. J., Matsushime, H., Kato, J.-Y., & Livingston, D. M. (1993) · Cell · doi:10.1016/0092-8674(93)90136-e · Cited by 1,010 · see citing works
A family of human cdc2‐related protein kinases.
Meyerson, M. M., Enders, G. H., Wu, C. L., Su, L., Gorka, C., Nelson, C. E., Harlow, E., & Tsai, L. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05360.x · Cited by 925 · see citing works
Matsushime, H., Ewen, M. E., Strom, D. K., Kato, J.-Y., Hanks, S. K., Roussel, M. F., & Sherr, C. J. (1992) · Cell · doi:10.1016/0092-8674(92)90360-o · Cited by 897 · see citing works
Kunz, J., Henríquez, R., Schneider, U., Deuter‐Reinhard, M., Movva, N. R., & Hall, M. N. (1993) · Cell · doi:10.1016/0092-8674(93)90144-f · Cited by 838 · see citing works
Physical interaction of the retinoblastoma protein with human D cyclins
Dowdy, S. F., Hinds, P. W., Louie, K., Reed, S. I., Arnold, A., & Weinberg, R. A. (1993) · Cell · doi:10.1016/0092-8674(93)90137-f · Cited by 746 · see citing works
Bierer, B. E., Mattila, P. S., Standaert, R. F., Herzenberg, L. A., Burakoff, S. J., Crabtree, G. R., & Schreiber, S. L. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.23.9231 · Cited by 695 · see citing works
Self-citationRapamycin-Induced Inhibition of the 70-Kilodalton S6 Protein Kinase
Price, D. J., Grove, J. R., Calvo, V., Avruch, J., & Bierer, B. E. (1992) · Science · doi:10.1126/science.1380182 · Cited by 666 · see citing works
Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase
Kuo, C. J., Chung, J., Fiorentino, D. F., Flanagan, W. M., Blenis, J., & Crabtree, G. R. (1992) · Nature · doi:10.1038/358070a0 · Cited by 594 · see citing works
Dumont, F. J., Melino, M. R., Staruch, M. J., Koprak, S., Fischer, P. A., & SIGAL, N. H. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.4.1418 · Cited by 355 · see citing works
Probing Immunosuppressant Action with a Nonnatural Immunophilin Ligand
Bierer, B. E., Somers, P. K., Wandless, T. J., Burakoff, S. J., & Schreiber, S. L. (1990) · Science · doi:10.1126/science.1700475 · Cited by 351 · see citing works
Self-citationKoltin, Y., Faucette, L. F., Bergsma, D. J., Levy, M. A., Cafferkey, R., Koser, P. L., Johnson, R. K., & Livi, G. P. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.3.1718-1723.1991 · Cited by 249 · see citing works
Ajchenbaum, F., Ando, K., DeCaprio, J. A., & Griffin, J. D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53587-0 · Cited by 237 · see citing works
Elledge, S. J., Richman, R., Hall, F. L., Williams, R. T., Lodgson, N., & Harper, J. W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2907 · Cited by 224 · see citing works
Self-citationMorice, W. G., Brunn, G. J., Wiederrecht, G., Siekierka, J. J., & Abraham, R. T. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53755-8 · Cited by 180 · see citing works
Interleukin 2 stimulation of p70 S6 kinase activity is inhibited by the immunosuppressant rapamycin.
Calvo, V., Crews, C. M., Vik, T. A., & Bierer, B. E. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7571 · Cited by 163 · see citing works
Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro.
Connell‐Crowley, L., Solomon, M. J., Wei, N., & Harper, J. W. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.1.79 · Cited by 158 · see citing works
Wiederrecht, G., Brizuela, L., Elliston, K. O., SIGAL, N. H., & Siekierka, J. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.3.1029 · Cited by 98 · see citing works
Hall, F. L., Braun, R., Mihara, K., Fung, Y. K., Berndt, N., Carbonaro-Hall, D. A., & Vulliet, P. R. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47391-2 · Cited by 63 · see citing works
Self-citationEffects of Rapamycin on Cultured Hepatocyte Proliferation and Gene Expression
Francavilla, A., Carr, B. I., Starzl, T. E., Azzarone, A., Carrieri, G., & Zeng, Q. H. (1992) · Hepatology · doi:10.1002/hep.1840150520 · Cited by 56 · see citing works
Hall, F. L., Williams, R. T., Wu, L., WU, F., Carbonaro-Hall, D. A., Harper, J. W., & Warburton, D. (1993) · PubMed · Cited by 48 · see citing works
Self-citationG1 expression and multistage dynamics of cyclin A in human osteosarcoma cells.
Carbonaro-Hall, D. A., Williams, R. T., Li-jun, W., Warburton, D., Zeichner‐David, M., MacDougall, M. J., Tolo, & Hall, F. L. (1993) · PubMed · Cited by 30 · see citing works
Self-citationIdentification of a novel cyclin-like protein in human tumor cells.
Williams, R. T., Wu, L., Carbonaro-Hall, D. A., Tolo, V. T., & Hall, F. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52954-9 · Cited by 26 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053 · see citing works
Self-citationThoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803 · see citing works
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509 · see citing works
mTOR and cancer: insights into a complex relationship
Sabatini, D. M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1974 · Cited by 1,322 · see citing works
Sekulić, A., Hudson, C. C., Homme, J. L., Yin, P., Otterness, D. M., Karnitz, L. M., & Abraham, R. T. (2000) · PubMed · Cited by 708 · see citing works
Control of p70 S6 kinase by kinase activity of FRAP in vivo
Brown, E. J., Beal, P. A., Keith, C. T., Chen, J., Shin, T. B., & Schreiber, S. L. (1995) · Nature · doi:10.1038/377441a0 · Cited by 705 · see citing works
Self-citationSehgal, S. N. (1998) · Clinical Biochemistry · doi:10.1016/s0009-9120(98)00045-9 · Cited by 660 · see citing works
IMMUNOPHARMACOLOGY OF RAPAMYCIN
Abraham, R. T., & Wiederrecht, G. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.483 · Cited by 653 · see citing works
Rapamycin selectively represses translation of the "polypyrimidine tract" mRNA family.
Jefferies, H. B. J., Reinhard, C., Kozma, S. C., & Thomas, G. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.10.4441 · Cited by 623 · see citing works
Natural products in anticancer therapy
Ab, D. R. (2001) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(01)00063-7 · Cited by 606 · see citing works
Activation of the PI3K/Akt pathway and chemotherapeutic resistance
West, K. A., Castillo, S. S., & Dennis, P. A. (2002) · Drug Resistance Updates · doi:10.1016/s1368-7646(02)00120-6 · Cited by 583 · see citing works
Chen, J., Zheng, X. F., Brown, E. J., & Schreiber, S. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4947 · Cited by 556 · see citing works
Self-citationMarine Natural Products: A Source of Novel Anticancer Drugs
Khalifa, S. A. M., Elias, N., Farag, M. A., Chen, L., Saeed, A., Hegazy, M.-E. F., Moustafa, M. S., Abd El-Wahed, A., Al-Mousawi, S. M., Musharraf, S. G., et al. (2019) · Marine Drugs · doi:10.3390/md17090491 · Cited by 555 · see citing works
Koyama, H., Raines, E. W., Bornfeldt, K., Roberts, J. M., & Ross, R. (1996) · Cell · doi:10.1016/s0092-8674(00)81801-2 · Cited by 514 · see citing works
Mayer, C., Zhao, J., Yuan, X., & Grummt, I. (2004) · Genes & Development · doi:10.1101/gad.285504 · Cited by 506 · see citing works
CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest
Goel, S., DeCristo, M. J., McAllister, S. S., & Zhao, J. J. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.07.002 · Cited by 495 · see citing works
RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
Chiu, M. I., Katz, H., & Berlin, V (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12574 · Cited by 481 · see citing works
Mechanism of action of the immunosuppressant rapamycin
Dumont, F. J., & Su, Q. (1995) · Life Sciences · doi:10.1016/0024-3205(95)02233-3 · Cited by 356 · see citing works
Hashemolhosseini, S., Nagamine, Y., Morley, S., Desrivières, S., Merćep, L., & Ferrari, S. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14424 · Cited by 343 · see citing works
Stanfel, M. N., Shamieh, L. S., Kaeberlein, M. R., & Kennedy, B. K. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.06.007 · Cited by 339 · see citing works
Hosoi, H., Dilling, M. B., Shikata, T., Liu, L. N., Shu, L., Ashmun, R. A., Germain, G. S., Abraham, R. T., & Houghton, P. J. (1999) · PubMed · Cited by 310 · see citing works
Inhibitors of protein kinases and phosphatases
MacKintosh, C., & MacKintosh, R. W. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90127-9 · Cited by 264 · see citing works
Curcumin inhibits the mammalian target of rapamycin‐mediated signaling pathways in cancer cells
Beevers, C. S., Li, F., Liu, L., & Huang, S. (2006) · International Journal of Cancer · doi:10.1002/ijc.21932 · Cited by 256 · see citing works
Rapamycin: an anti-cancer immunosuppressant?
Law, B. K. (2005) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2004.09.009 · Cited by 252 · see citing works
Jacobs, T. W. (1995) · Annual Review of Plant Physiology and Plant Molecular Biology · doi:10.1146/annurev.pp.46.060195.001533 · Cited by 252 · see citing works
Immunophilins in protein folding and immunosuppression 1
Fruman, D. A., Burakoff, S. J., & Bierer, B. E. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.6.7513288 · Cited by 249 · see citing works
Peptidylproline cis/trans isomerases
Gałat, A., & Metcalfe, S. M. (1995) · Progress in Biophysics and Molecular Biology · doi:10.1016/0079-6107(94)00009-x · Cited by 240 · see citing works
The 70 kDa S6 kinase: regulation of a kinase with multiple roles in mitogenic signalling
Chou, M. M., & Blenis, J. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80064-6 · Cited by 237 · see citing works
TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin
Lorenz, M. C., & Heitman, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27531 · Cited by 236 · see citing works
Dudkin, L., Dilling, M. B., Cheshire, P. J., Harwood, F. C., Hollingshead, M. G., Arbuck, S. G., Travis, R., Sausville, E. A., & Houghton, P. J. (2001) · PubMed · Cited by 232 · see citing works
Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells.
Yeh, W., Bierer, B. E., & McKnight, S. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11086 · Cited by 226 · see citing works
Rapamycin Resistance Tied to Defective Regulation of p27 Kip1
Luo, Y., Marx, S. O., Kiyokawa, H., Koff, A., Massagué, J., & Marks, A. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.12.6744 · Cited by 210 · see citing works
Averous, J., Fonseca, B. D., & Proud, C. G. (2008) · Oncogene · doi:10.1038/sj.onc.1210715 · Cited by 194 · see citing works
Understanding and controlling the cell cycle with natural products
Hung, D. T., Jamison, T. F., & Schreiber, S. L. (1996) · Chemistry & Biology · doi:10.1016/s1074-5521(96)90129-5 · Cited by 183 · see citing works
Self-citationSingha, U. K., Jiang, Y., Yu, S., Luo, M., Lu, Y., Zhang, J., & Xiao, G. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21411 · Cited by 180 · see citing works
FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition
Baughman, G., Wiederrecht, G. J., Campbell, N. F., Martin, M. M., & Bourgeois, S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4395 · Cited by 173 · see citing works
The p70 S6 Kinase Integrates Nutrient and Growth Signals to Control Translational Capacity
Avruch, J., BELHAM, C. M., Weng, Q. P., Hara, K., & Yonezawa, K. (2001) · Progress in molecular and subcellular biology · doi:10.1007/978-3-642-56688-2_5 · Cited by 175 · see citing works
Vilella-Bach, M., Nuzzi, P., Fang, Y., & Chen, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.7.4266 · Cited by 154 · see citing works
Defect in Multiple Cell Cycle Checkpoints in Ataxia-Telangiectasia Postirradiation
Beamish, H., Williams, R. T., Chen, P., & Lavin, M. F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20486 · Cited by 137 · see citing works
Self-citationMechanisms of resistance to rapamycins
Huang, S., & Houghton, P. J. (2001) · Drug Resistance Updates · doi:10.1054/drup.2002.0227 · Cited by 136 · see citing works
The Biological Role of PI3K Pathway in Lung Cancer
Sarris, E., Saif, M. W., & Syrigos, K. (2012) · Pharmaceuticals · doi:10.3390/ph5111236 · Cited by 127 · see citing works
Cell Replication in the Arterial Wall
Koyama, H., Olson, N. E., Dastvan, F., & Reidy, M. A. (1998) · Circulation Research · doi:10.1161/01.res.82.6.713 · Cited by 127 · see citing works
Mammalian anti proliferative signals and their targets
Massagué, J., & Polyák, K. (1995) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(95)90059-4 · Cited by 123 · see citing works
From Beach to Bedside: History of the Development of Sirolimus
Napoli, K. L., & Taylor, P. J. (2001) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200110000-00012 · Cited by 118 · see citing works
Yellen, P., Saqcena, M., Salloum, D., Feng, J., Preda, A., Xu, L., Rodrik-Outmezguine, V. S., & Foster, D. A. (2011) · Cell Cycle · doi:10.4161/cc.10.22.18124 · Cited by 117 · see citing works
Ito, D., Fujimoto, K., Mori, T., Kami, K., Koizumi, M., Toyoda, E., Kawaguchi, Y., & Doi, R. (2005) · International Journal of Cancer · doi:10.1002/ijc.21532 · Cited by 117 · see citing works
The Upregulation of p27Kip1 by Rapamycin Results in G1 Arrest in Exponentially Growing T-Cell Lines
Kawamata, S., Sakaida, H., Hori, T., Maeda, M., & Uchiyama, T. (1998) · Blood · doi:10.1182/blood.v91.2.561 · Cited by 117 · see citing works
Cardenas, M. E., & Heitman, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00277.x · Cited by 116 · see citing works
The Potential Role of mTOR Inhibitors in Non-Small Cell Lung Cancer
Gridelli, C., Maione, P., & Rossi, A. (2008) · The Oncologist · doi:10.1634/theoncologist.2007-0171 · Cited by 106 · see citing works
Cerovac, V., Garcia, J. L. M., Rubinfeld, H., Buchfelder, M., Losa, M., Florio, T., Páez-Pereda, M., Stalla, G. K., & Theodoropoulou, M. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2951 · Cited by 104 · see citing works
Skotzko, M. J., Wu, L., Anderson, W. F., Gordon, E. M., & Hall, F. L. (1995) · PubMed · Cited by 102 · see citing works
Self-citationControl of Translation by the Target of Rapamycin Proteins
Gingras, A., Raught, B., & Sonenberg, N. (2001) · Progress in molecular and subcellular biology · doi:10.1007/978-3-662-09889-9_6 · Cited by 99 · see citing works
Dilling, M. B., Germain, G. S., Dudkin, L., Jayaraman, A. L., Zhang, X., Harwood, F. C., & Houghton, P. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110782200 · Cited by 96 · see citing works
Inhibitors of the mammalian target of rapamycin
Dancey, J. E. (2005) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.14.3.313 · Cited by 95 · see citing works
Molecular characterization of a FKBP-type immunophilin from higher plants.
Luan, S., Kudla, J., Gruissem, W., & Schreiber, S. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.6964 · Cited by 91 · see citing works
Self-citationRelationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3-kinase
Lavin, M. F., Khana, K. K., Beamish, H., Spring, K. J., Watters, D. J., & Shiloh, Y. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89083-0 · Cited by 84 · see citing works
The Rapamycin and FKBP12 Target (RAFT) Displays Phosphatidylinositol 4-Kinase Activity
Sabatini, D. M., Pierchala, B. A., Barrow, R. K., Schell, M. J., & Snyder, S. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.20875 · Cited by 82 · see citing works
Rapamycin specifically interferes with the developmental response of fission yeast to starvation
Weisman, R., Choder, M., & Koltin, Y. (1997) · Journal of Bacteriology · doi:10.1128/jb.179.20.6325-6334.1997 · Cited by 75 · see citing works
The Immunosuppressant Rapamycin Represses Human Immunodeficiency Virus Type 1 Replication
Roy, J., Paquette, J., Fortin, J., & Tremblay, M. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.11.3447-3455.2002 · Cited by 79 · see citing works
Beta-lactams and their potential use as novel anticancer chemotherapeutics drugs
Kuhn, D. J. (2004) · Frontiers in bioscience · doi:10.2741/1420 · Cited by 74 · see citing works
Casagrande, F., Bacqueville, D., Pillaire, M., Malecaze, F., Manenti, S., Breton, M., & Darbon, J.-M. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00043-x · Cited by 74 · see citing works
FK506 binding protein 12 mediates sensitivity to both FK506 and rapamycin in murine mast cells
Fruman, D. A., Wood, M. A., Gjertson, C. K., Katz, H. R., Burakoff, S. J., & Bierer, B. E. (1995) · European Journal of Immunology · doi:10.1002/eji.1830250239 · Cited by 72 · see citing works
Law, M. E., Forrester, E., Chytil, A. M., Corsino, P. E., Green, G., Davis, B. J., Rowe, T. C., & Law, B. K. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-1672 · Cited by 66 · see citing works
Signaling by the transforming growth factor-β receptor
Yingling, J. M., Wang, X., & Bassing, C. H. (1995) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(95)00007-2 · Cited by 65 · see citing works
Potential Prospect of CDK4/6 Inhibitors in Triple-Negative Breast Cancer
Hu, Y., Gao, J., Wang, M., & Li, M. (2021) · Cancer Management and Research · doi:10.2147/cmar.s310649 · Cited by 64 · see citing works
Rapamycin, proliferation and geroconversion to senescence
Blagosklonny, M. V. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1554781 · Cited by 61 · see citing works
Zhu, N. L., Wu, L., Liu, P. X., Gordon, E. M., Anderson, W. F., Starnes, V. A., & Hall, F. L. (1997) · Circulation · doi:10.1161/01.cir.96.2.628 · Cited by 61 · see citing works
Self-citationPhosphatidylinositol 3-kinase related kinases
Abraham, R. T. (1996) · Current Opinion in Immunology · doi:10.1016/s0952-7915(96)80132-4 · Cited by 58 · see citing works
Results of a phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma
Schuetze, S. M., Zhao, L., Chugh, R. K., Thomas, D. G., Lucas, D. R., Metko, G., Zalupski, M. M., & Baker, L. H. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.03.022 · Cited by 52 · see citing works
Mu, X., Isaac, C. E., Schott, T., Huard, J., & Weiss, K. R. (2013) · Sarcoma · doi:10.1155/2013/480713 · Cited by 50 · see citing works
Cdc42 Promotes G1 Progression through p70 S6 Kinase-mediated Induction of Cyclin E Expression
Chou, M. M., Robens, J., & Gupta, M. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305246200 · Cited by 51 · see citing works
Odaka, Y., Xu, B., Luo, Y., Shen, T., Shang, C., Wu, Y., Zhou, H., & Huang, S. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt277 · Cited by 50 · see citing works
Quesniaux, V. F. J., Wehrli, S., Steiner, C. W., Joergensen, J., Schuurman, H., Herrman, P., Schreier, M., & Schüler, W. (1994) · Blood · doi:10.1182/blood.v84.5.1543.1543 · Cited by 50 · see citing works
Translation initiation: a critical signalling node in cancer
Robert, F., & Pelletier, J. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903241625 · Cited by 48 · see citing works
Feuerstein, N., Huang, D., & Prystowsky, M. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9454 · Cited by 47 · see citing works
Zhao, M. Y., Auerbach, A., D'Costa, A. M., Rapoport, A. P., Burger, A. M., Sausville, E. A., Stass, S. A., Jiang, F., Sands, A. M., Aguilera, N. S. I., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1543 · Cited by 45 · see citing works
Kristof, A. S., Pacheco–Rodriguez, G., Schremmer, B., & Moss, J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.083550 · Cited by 45 · see citing works
Evidence for Cyclin D3 as a Novel Target of Rapamycin in Human T Lymphocytes
Hleb, M., Murphy, S., Wagner, E. F., Hanna, N. N., Sharma, N., Park, J., Li, X. C., Strom, T. B., Padbury, J. F., Tseng, Y., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400638200 · Cited by 45 · see citing works
Dhakal, A., Thomas, R. A., Levine, E. G., Brufsky, A., Takabe, K., Hanna, M. G., Attwood, K. M., Miller, A., Khoury, T., Early, A., et al. (2020) · Breast Cancer Basic and Clinical Research · doi:10.1177/1178223420944864 · Cited by 42 · see citing works
Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast.Preprint
Alarcón, C. M., Cardenas, M. E., & Heitman, J. (1996) · Genes & Development · doi:10.1101/gad.10.3.279 · Cited by 42 · see citing works
Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer cells
García-Morales, P., Hernando, E., Carrasco‐García, E., Menéndez-Gutierrez, M. P., Saceda, M., & Martínez-Lacaci, I. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0363 · Cited by 38 · see citing works
Banholzer, R., Nair, A. P. K., Hirsch, H. H., Ming, X., & Moroni, C. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3254 · Cited by 35 · see citing works
Yamamoto-Yamaguchi, Y., Okabe‐Kado, J., Kasukabe, T., & Honma, Y. (2001) · Experimental Hematology · doi:10.1016/s0301-472x(01)00626-9 · Cited by 34 · see citing works
Canicio, J., Gallardo, E., Illa, I., Testar, X., Palacín, M., Zorzano, A., & Kaliman, P. (1998) · Endocrinology · doi:10.1210/endo.139.12.6360 · Cited by 35 · see citing works
Dhakal, A., Matthews, C. M., Levine, E. G., Salerno, K. E., Zhang, F., Takabe, K., Early, A., Edge, S. B., O'Connor, T., Khoury, T., et al. (2018) · Clinical Breast Cancer · doi:10.1016/j.clbc.2018.04.015 · Cited by 33 · see citing works
Stankunas, K., Bayle, J. H., Havranek, J. J., Wandless, T. J., Baker, D. A., Crabtree, G. R., & Gestwicki, J. E. (2007) · ChemBioChem · doi:10.1002/cbic.200700087 · Cited by 33 · see citing works
mTOR inhibition sensitizes gastric cancer to alkylating chemotherapy in vivo.
Cejka, D., Preusser, M., Fuereder, T., Sieghart, W., Werzowa, J. M., Strommer, S., & Wacheck, V. (2008) · PubMed · Cited by 30 · see citing works
Farnesylthiosalicylic acid blocks mammalian target of rapamycin signaling in breast cancer cells
Yue, W., Wang, J., Li, Y., Fan, P., & Santen, R. J. (2005) · International Journal of Cancer · doi:10.1002/ijc.21222 · Cited by 31 · see citing works
Johnson, K. L., & Lawen, A. (1999) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.1999.00821.x · Cited by 30 · see citing works
Growth inhibitory effects of FK506 and cyclosporin A independent of inhibition of calcineurin
Richter, A., Davies, D. E., & Alexander, P. M. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(94)00423-j · Cited by 30 · see citing works
Negative Growth Regulation of SK-N-MC Cells by bFGF Defines a Growth Factor-sensitive Point in G2
Smits, V. A. J., van Peer, M. A., Essers, M. A. G., Klompmaker, R., Rijksen, G., & Medema, R. H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001764200 · Cited by 29 · see citing works
Preclinical results of sirolimus treatment in transplant models
Stepkowski, S. M. (2003) · Transplantation Proceedings · doi:10.1016/s0041-1345(03)00222-7 · Cited by 28 · see citing works
Estrogen and rapamycin effects on cell cycle progression in T47D breast cancer cells
Pang, H., & Faber, L. E. (2001) · Breast Cancer Research and Treatment · doi:10.1023/a:1012570204923 · Cited by 26 · see citing works
Mekonnen, L. B., Tadesse, S., Lenjisa, J. L., Yu, M., Noll, B. D., Heinemann, G. K., Lokman, N. A., Ricciardelli, C., Oehler, M. K., Beck, A. R., et al. (2020) · Gynecologic Oncology · doi:10.1016/j.ygyno.2020.09.012 · Cited by 25 · see citing works
Formica, R. N., Lorber, K. M., Friedman, A. L., BIA, M. J., Lakkis, F. G., Smith, J. D., & Lorber, M. I. (2003) · Transplantation Proceedings · doi:10.1016/s0041-1345(03)00216-1 · Cited by 23 · see citing works
Immunosuppressive Drugs in HIV Disease
Argyropoulos, C., & Mouzaki, Α. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802606778194271 · Cited by 23 · see citing works
Wood, M. A., & Bierer, B. E. (1994) · Perspectives in Drug Discovery and Design · doi:10.1007/bf02171742 · Cited by 21 · see citing works
Role of NF-kappaB in the control of apoptotic and proliferative responses in IL-2-responsive T cells
Martínez‐A, C. (1997) · Frontiers in bioscience · doi:10.2741/a174 · Cited by 20 · see citing works
Iwabuchi, T. (1995) · Journal of Dermatological Science · doi:10.1016/0923-1811(94)00351-e · Cited by 20 · see citing works
Morrow, P. W., Tung, H. Y. L., & Hemmings, H. C. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.08.147 · Cited by 19 · see citing works
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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