Cited by 887PI3K/AKT/mTOR signaling in cancerSignaling Pathways in DiseaseAutophagy in Disease and Therapy

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells

Open access

Sabers, Candace J., Martin, Mary M., Brunn, Gregory J., Williams, Josie M., Dumont, Francis J., Wiederrecht, Gregory, Abraham, Robert T.·1995·Journal of Biological Chemistry

DOI 10.1074/jbc.270.2.815

Open this paper in CoChat — free account Open PDF

Abstract

The immunosuppressive drug, rapamycin, interferes with an undefined signaling pathway required for the progression of G1-phase T-cells into S phase. Genetic analyses in yeast indicate that binding of rapamycin to its intracellular receptor, FKBP12, generates a toxic complex that inhibits cell growth in G1 phase. These analyses implicated two related proteins, TOR1 and TOR2, as targets of the FKBP12-rapamycin complex in yeast. In this study, we have used a glutathione S-transferase (GST)-FKBP12-rapamycin affinity matrix to isolate putative mammalian targets of rapamycin (mTOR) from tissue extracts. In the presence of rapamycin, immobilized GST-FKBP12 specifically precipitates similar high molecular mass proteins from both rat brain and murine T-lymphoma cell extracts. Binding experiments performed with rapamycin-sensitive and -resistant mutant clones derived from the YAC-1 T-lymphoma cell line demonstrate that the GST-FKBP12-rapamycin complex recovers significantly lower amounts of the candidate mTOR from rapamycin-resistant cell lines. The latter results suggest that mTOR is a relevant target of rapamycin in these cells. Finally, we report the isolation of a full-length mTOR cDNA that encodes a direct ligand for the FKBP12-rapamycin complex. The deduced amino acid sequence of mTOR displays 42 and 45% identity to those of yeast TOR1 and TOR2, respectively. These results strongly suggest that the FKBP12-rapamycin complex interacts with homologous ligands in yeast and mammalian cells and that the loss of mTOR function is directly related to the inhibitory effect of rapamycin on G1- to S-phase progression in T-lymphocytes and other sensitive cell types.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1074/jbc.270.2.815

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
A comprehensive set of sequence analysis programs for the VAX
Devereux, J., Haeberli, P. E., & Smithies, O. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.1part1.387 · Cited by 14,222
An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs
Kozak, M. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.20.8125 · Cited by 5,090
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
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
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
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
Clipstone, N. A., & Crabtree, G. R. (1992) · Nature · doi:10.1038/357695a0 · Cited by 1,635
RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs
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
In-gel digestion of proteins for internal sequence analysis after one- or two-dimensional gel electrophoresis
Rosenfeld, J., Capdevielle, J., Guillemot, J. C., & Ferrara, P. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90061-b · Cited by 1,239
Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases
Chung, J., Kuo, C. J., Crabtree, G. R., & Blenis, J. (1992) · Cell · doi:10.1016/0092-8674(92)90643-q · Cited by 1,151

Flagged first, then by citations

Show all 29 references

Research works printed but not linked: 1

Cafferkey, 1993, Mol. Cell. Biol., 13, 6012, 10.1128/MCB.13.10.6012 · DOI

Sorted by citations

Items 401–500 of 885

Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas
Drakos, E., Rassidakis, G. Z., & Medeiros, L. J. (2008) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399408000586 · Cited by 55
In Rat Hepatocytes Glucagon Increases Mammalian Target of Rapamycin Phosphorylation on Serine 2448 but Antagonizes the Phosphorylation of Its Downstream Targets Induced by Insulin and Amino Acids
Mothe‐Satney, I., Gautier, N., Hinault, C., Lawrence, J. C., & OBBERGHEN, E. V. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405173200 · Cited by 53
lnterleukin-2 Receptor Signaling Mechanisms
Karnitz, L. M., & Abraham, R. T. (1996) · Advances in immunology · doi:10.1016/s0065-2776(08)60867-6 · Cited by 53
Self-citation
Targeted therapy of cancer stem cells: inhibition of mTOR in pre-clinical and clinical research
Son, B., Lee, W., Kim, H., Shin, H., & Park, H. H. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07077-8 · Cited by 55
Rapamycin Blocks Sexual Development in Fission Yeast through Inhibition of the Cellular Function of an FKBP12 Homolog
Weisman, R., Finkelstein, S., & Choder, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102090200 · Cited by 52
Genetic susceptibility to cancer: ICRP Publication 79
Approved by the Commission in May 1997 (1998) · Annals of the ICRP · doi:10.1016/s0146-6435(98)00007-3 · Cited by 54
mTOR Inhibition: From Aging to Autism and Beyond
Kaeberlein, M. R. (2013) · Scientifica · doi:10.1155/2013/849186 · Cited by 52
The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals
Tan, H. K., Moad, A. I. H., & Tan, M. L. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.16.6463 · Cited by 51
Robust LC3B lipidation analysis by precisely adjusting autophagic flux
Liebl, M. P., Meister, S. C., Frey, L., Hendrich, K., Klemmer, A., Wohlfart, B., Untucht, C., Nuber, J., Pohl, C., & Lakics, V. (2022) · Scientific Reports · doi:10.1038/s41598-021-03875-8 · Cited by 51
Induced proximity-based therapeutic modalities
King, E. A., Meyers, M., & Nomura, D. K. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01316-z · Cited by 61
Rapamycin Inhibits ALDH Activity, Resistance to Oxidative Stress, and Metastatic Potential in Murine Osteosarcoma Cells
Mu, X., Isaac, C. E., Schott, T., Huard, J., & Weiss, K. R. (2013) · Sarcoma · doi:10.1155/2013/480713 · Cited by 50
Tissue-resident dendritic cells and diseases involving dendritic cell malfunction
Chen, K., Wang, J., Yuan, R., Xiang, Y., Li, L., Gong, W., Yang, T., Li, L., & Su, S. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.02.007 · Cited by 51
Cycloheximide promotes paraptosis induced by inhibition of cyclophilins in glioblastoma multiforme
Wang, L., Gundelach, J. H., & Bram, R. J. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.217 · Cited by 50
Discovery of Small-Molecule Selective mTORC1 Inhibitors via Direct Inhibition of Glucose Transporters
Kang, S. A., O’Neill, D. J., Machl, A. W., Lumpkin, C. J., Galda, S. N., Sengupta, S., Mahoney, S. J., Howell, J. J., Molz, L., Hahm, S., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.05.009 · Cited by 50
Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment
Hage, A., & Dormond, O. (2021) · Cancers · doi:10.3390/cancers13061359 · Cited by 51
Ex Vivo Rapamycin Generates Th1/Tc1 or Th2/Tc2 Effector T Cells With Enhanced In Vivo Function and Differential Sensitivity to Post-transplant Rapamycin Therapy
Jung, U., Foley, J., Erdmann, A. A., Toda, Y., Borenstein, T., Mariotti, J., & Fowler, D. H. (2006) · Transplantation and Cellular Therapy · doi:10.1016/j.bbmt.2006.05.014 · Cited by 50
Insulin Regulation of Hepatic Lipid Homeostasis
Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023) · Comprehensive Physiology · doi:10.1002/cphy.c220015 · Cited by 49
Regulation of mTORC1 by the Rag GTPases
Lama-Sherpa, T. D., Jeong, M., & Jewell, J. L. (2023) · Biochemical Society Transactions · doi:10.1042/bst20210038 · Cited by 52
DAP1, a Negative Regulator of Autophagy, Controls SubAB-Mediated Apoptosis and Autophagy
Yahiro, K., Tsutsuki, H., Ogura, K., Nagasawa, S., Moss, J., & Noda, M. (2014) · Infection and Immunity · doi:10.1128/iai.02213-14 · Cited by 49
DEPDC5 as a potential therapeutic target for epilepsy
Myers, K. A., & Scheffer, I. E. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1316715 · Cited by 50
HLXB9 activates IL6 in Hodgkin lymphoma cell lines and is regulated by PI3K signalling involving E2F3
Nagel, S., Scherr, M., Quentmeier, H., Kaufmann, M., Zaborski, M., Drexler, H. G., & MacLeod, R. A. F. (2005) · Leukemia · doi:10.1038/sj.leu.2403716 · Cited by 49
Mammalian target of rapamycin (mTOR): a central regulator of male fertility?
Jesus, T. T., Oliveira, P. F., Sousa, M., Cheng, C. Y., & Alves, M. G. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1279120 · Cited by 50
Functional diversity and pharmacological profiles of the FKBPs and their complexes with small natural ligands
Gałat, A. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1206-z · Cited by 48
Kinase Activities Associated with mTOR
Yonezawa, K., Yoshino, K., Tokunaga, C., & Hara, K. (2004) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-18930-2_16 · Cited by 48
Synergism between sirolimus and 1,25-dihydroxyvitamin D3 in vitro and in vivo
Brǎnişteanu, D. D. D., Mathieu, C., & Bouillon, R. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(97)00116-1 · Cited by 48
mTOR signalling, embryogenesis and the control of lung development
Land, S. C., Scott, C. L., & Walker, D. J. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.09.023 · Cited by 50
Chemical Inhibitors and microRNAs (miRNA) Targeting the Mammalian Target of Rapamycin (mTOR) Pathway: Potential for Novel Anticancer Therapeutics
Alqurashi, N., Hashimi, S. M., & Wei, M. Q. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14023874 · Cited by 47
Sirolimus as a new drug to treat RIF patients with elevated Th17/Treg ratio: A double-blind, phase II randomized clinical trial
Ahmadi, M., Abdolmohammadi‐Vahid, S., Ghaebi, M., Dolati, S., Abbaspour‐Aghdam, S., Danaii, S., Berjis, K., Madadi-Javid, R., Nouri, Z., Siahmansouri, H., et al. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105730 · Cited by 47
The Importance of mTORC1-Autophagy Axis for Skeletal Muscle Diseases
Han, X., Goh, K. Y., Lee, W. X., Choy, S. M., & Tang, H.-W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010297 · Cited by 48
A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets
Zhou, P., Chan, B. K. C., Wan, Y. K., Yuen, C. T. L., Choi, G. C. G., Li, X., Tong, C. S. W., Zhong, S. S. W., Sun, J., Bao, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108020 · Cited by 46
The Involvement of Mammalian and Plant FK506-Binding Proteins (FKBPs) in Development
Breiman, A., & Camus, I. (2002) · Transgenic Research · doi:10.1023/a:1016331814412 · Cited by 47
Uncoupling p70s6 Kinase Activation and Proliferation: Rapamycin-Resistant Proliferation of Human CD8+ T Lymphocytes
Slavik, J. M., Lim, D., Burakoff, S. J., & Hafler, D. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.5.3201 · Cited by 46
Cortical Dysplasia and the mTOR Pathway: How the Study of Human Brain Tissue Has Led to Insights into Epileptogenesis
Lee, W. S., Baldassari, S., Stephenson, S. E. M., Lockhart, P. J., Baulac, S., & Leventer, R. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031344 · Cited by 45
Exploring mammalian target of rapamycin (mTOR) inhibition for treatment of mantle cell lymphoma and other hematologic malignancies
Coiffier, B., & Ribrag, V. (2009) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190903207548 · Cited by 45
BCLB, methylated in hepatocellular carcinoma, is a starvation stress sensor that induces apoptosis and autophagy through the AMPK-mTOR signaling cascade
Liu, X., Hu, X., Kuang, Y., Yan, P., Li, L., Li, C., Tao, Q., & Cai, X. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.02.030 · Cited by 45
Rapamycin stimulates viral protein synthesis and augments the shutoff of host protein synthesis upon picornavirus infection
Beretta, L., Svitkin, Y. V., & Sonenberg, N. (1996) · Journal of Virology · doi:10.1128/jvi.70.12.8993-8996.1996 · Cited by 45
Chemical Genomics: A Systematic Approach in Biological Research and Drug Discovery
Zheng, X. F. S., & Chan, T. (2002) · Current Issues in Molecular Biology · doi:10.21775/cimb.004.033 · Cited by 45
Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health
Wang, G., Chen, L., Qin, S., Zhang, T., Yao, J., Yi, Y., & Deng, L. (2022) · Advances in Nutrition · doi:10.1093/advances/nmac055 · Cited by 45
Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals
Morozumi, Y., & Shiozaki, K. (2021) · Genes · doi:10.3390/genes12010088 · Cited by 44
Involvement of the Akt/mTOR pathway on EGF‐induced cell transformation
Nomura, M., He, Z., Koyama, I., Ma, W., Miyamoto, K., & Dong, Z. (2003) · Molecular Carcinogenesis · doi:10.1002/mc.10140 · Cited by 44
Resistance to Rapamycin: A Novel Anticancer Drug
Huang, S., & Houghton, P. J. (2001) · Cancer and Metastasis Reviews · doi:10.1023/a:1013167315885 · Cited by 44
Insulin Receptor Substrate-2-dependent Interleukin-4 Signaling in Macrophages Is Impaired in Two Models of Type 2 Diabetes Mellitus
Hartman, M. E., O’Connor, J. C., Godbout, J. P., Minor, K. D., Mazzocco, V. R., & Freund, G. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404368200 · Cited by 45
The zinc finger protein GLI induces cellular sensitivity to the mTOR inhibitor rapamycin.
Louro, I. D., McKie-Bell, P., Gosnell, H., Brindley, B. C., Bucy, R. P., & Ruppert, J. M. (1999) · PubMed · Cited by 44
Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells
Miyake, N., Chikumi, H., Takata, M., Nakamoto, M., Igishi, T., & Shimizu, E. (2012) · Oncology Reports · doi:10.3892/or.2012.1855 · Cited by 44
A natural product solution to aging and aging-associated diseases
Yang, C., Zhang, W., Dong, X., Fu, C., Yuan, J., Xu, M., Liang, Z. C., Qiu, C., & Xu, C. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107673 · Cited by 43
The Role of Targeting Mammalian Target of Rapamycin in Lung Cancer
Pal, S. K., Figlin, R. A., & Reckamp, K. L. (2008) · Clinical Lung Cancer · doi:10.3816/clc.2008.n.049 · Cited by 43
The Central Role of mTORC1 in Amino Acid Sensing
Yue, S., Li, G., He, S., & Li, T. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-4403 · Cited by 45
Game of TOR — The Target of Rapamycin Rules Four Kingdoms
Manning, B. D. (2017) · New England Journal of Medicine · doi:10.1056/nejmcibr1709384 · Cited by 42
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
Rapamycin generates anti-apoptotic human Th1/Tc1 cells via autophagy for induction of xenogeneic GVHD
Amarnath, S., Flomerfelt, F. A., Costanzo, C. M., Foley, J., Mariotti, J., Konecki, D. M., Gangopadhyay, A., Eckhaus, M., Wong, S., Levine, B. L., et al. (2010) · Autophagy · doi:10.4161/auto.6.4.11811 · Cited by 41
Chemical genomics in the global study of protein functions
Zheng, X.-F., & Chan, T. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(01)02118-3 · Cited by 41
The Role of Activation of PI3K/AKT/mTOR and RAF/MEK/ERK Pathways in Aggressive Pituitary Adenomas—New Potential Therapeutic Approach—A Systematic Review
Derwich-Rudowicz, A., Sykutera, M., Bromińska, B., Rubiś, B., Ruchała, M., & Sawicka‐Gutaj, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310952 · Cited by 40
Biotic acts of antibiotics
Aminov, R. I. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00241 · Cited by 40
Pharmacological Targeting of Catalyzed Protein Folding: The Example of Peptide Bond cis/trans Isomerases
Edlich, F., & Fischer, G. S. (2005) · Handbook of experimental pharmacology · doi:10.1007/3-540-29717-0_15 · Cited by 40
SPLINTS: small-molecule protein ligand interface stabilizers
Fischer, E. S., Park, E., Eck, M. J., & Thomä, N. H. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.01.004 · Cited by 39
Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training
Solsona, R., Pavlin, L., Bernardi, H., & Sanchez, A. M. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052741 · Cited by 42
Functional Drift of Sequence Attributes in the FK506-Binding Proteins (FKBPs)
Gałat, A. (2008) · Journal of Chemical Information and Modeling · doi:10.1021/ci700429n · Cited by 39
Effect of rapamycin on the cyclosporin A–resistant CD28-mediated costimulatory pathway
Ghosh, P., Buchholz, M. A., Yano, S., Taub, D. D., & Longo, D. L. (2002) · Blood · doi:10.1182/blood-2001-11-0062 · Cited by 39
Sensors for the mTORC1 pathway regulated by amino acids
Li, X.-Z., & Yan, X. (2019) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1900181 · Cited by 41
Highly efficient osteogenic differentiation of human mesenchymal stem cells by eradication of STAT3 signaling
Levy, O., Ruvinov, E., Re’em, T. T., Granot, Y., & Cohen, S. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.07.017 · Cited by 40
Identification of functional FKB protein in Echinococcus granulosus: Its involvement in the protoscolicidal action of rapamycin derivates and in calcium homeostasis
Cumino, A. C., Lamenza, P., & Denegri, G. M. (2009) · International Journal for Parasitology · doi:10.1016/j.ijpara.2009.11.011 · Cited by 38
An Emerging Role for the Mammalian Target of Rapamycin in “Pathological” Protein Translation: Relevance to Cocaine Addiction
Dayas, C. V., Smith, D. W., & Dunkley, P. R. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00013 · Cited by 44
The FKBP-associated protein FAP48 is an antiproliferative molecule and a player in T cell activation that increases IL2 synthesis
Krummrei, U., Baulieu, É.-É., & Chambraud, B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0438007100 · Cited by 38
FKBP12 Physically and Functionally Interacts with Aspartokinase in Saccharomyces cerevisiae
Alarcón, C. M., & Heitman, J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.10.5968 · Cited by 38
Calcium/calmodulin kinase inhibitors and immunosuppressant macrolides rapamycin and FK506 inhibit progestin- and glucocorticosteroid receptor-mediated transcription in human breast cancer T47D cells.
Le Bihan, S., Marsaud, V., Mercier-Bodard, C., Baulieu, E.-E., Mader, S., White, J. H., & Renoir, J.-M. (1998) · Molecular Endocrinology · doi:10.1210/mend.12.7.0128 · Cited by 37
FKBPs in bacterial infections
Ünal, C., & Steinert, M. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.12.018 · Cited by 37
Targeting kinases with thymoquinone: a molecular approach to cancer therapeutics
Afrose, S. S., Junaid, M., Akter, Y., Tania, M., Zheng, M., & Khan, M. A. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.07.019 · Cited by 37
Autophagy dysregulation and the fate of retinal ganglion cells in glaucomatous optic neuropathy
Russo, R., Nucci, C., Corasaniti, M. T., Bagetta, G., & Morrone, L. A. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.04.009 · Cited by 37
FRAP-Dependent Serine Phosphorylation of IRS-1 Inhibits IRS-1 Tyrosine Phosphorylation
Hartman, M. E., Villela-Bach, M., Chen, J., & Freund, G. G. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.4214 · Cited by 37
Secretion of FK506/FK520 and rapamycin by Streptomyces inhibits the growth of competing Saccharomyces cerevisiae and Cryptococcus neoformans
Arndt, C., Cruz, M. C., Cardenas, M. E., & Heitman, J. (1999) · Microbiology · doi:10.1099/13500872-145-8-1989 · Cited by 37
Activation of the mTOR pathway by the amino acid l-leucine in the 5q- syndrome and other ribosomopathies
Boultwood, J., Yip, B. H., Vuppusetty, C., Pellagatti, A., & Wainscoat, J. S. (2012) · Advances in Biological Regulation · doi:10.1016/j.jbior.2012.09.002 · Cited by 36
Hmo1p, a High Mobility Group 1/2 Homolog, Genetically and Physically Interacts With the Yeast FKBP12 Prolyl Isomerase
Dolinski, K. J., & Heitman, J. (1999) · Genetics · doi:10.1093/genetics/151.3.935 · Cited by 36
Amino acid and small GTPase regulation of mTORC1
Nguyen, T. P., Frank, A. R., & Jewell, J. L. (2017) · Cellular Logistics · doi:10.1080/21592799.2017.1378794 · Cited by 37
Metabolic pathways mediate pathogenesis and offer targets for treatment in rheumatic diseases
Wyman, B., & Perl, A. (2019) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000687 · Cited by 35
Methods for Studying Signal‐Dependent Regulation of Translation Factor Activity
Wang, X., & Proud, C. G. (2007) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)31007-0 · Cited by 35
Nutrient sensing of mTORC1 signaling in cancer and aging
Jiang, C., Tan, X., Liu, N., Yan, P., Hou, T., & Wei, W. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.08.001 · Cited by 35
Transcriptional and Epigenetic Regulation by the Mechanistic Target of Rapamycin Complex 1 Pathway
Laribee, R. N. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.10.008 · Cited by 37
Targeting the mTOR regulatory network in hepatocellular carcinoma: Are we making headway?
Yu, X., Chen, H., Liu, T., Wu, J. H., Zhu, J., & Shen, X. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.03.001 · Cited by 34
Nanotechnology-Based Targeting of mTOR Signaling in Cancer
Yoon, M. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s254574 · Cited by 35
Novel Regulatory Mechanisms of mTOR Signaling
Chen, J. (2004) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-18930-2_14 · Cited by 34
Targeting mTOR-mediated survival signals in anticancer therapeutic strategies
Foster, D. A. (2004) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.4.4.691 · Cited by 34
Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease
Shi, F., & Collins, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411497 · Cited by 34
The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb
Feng, R., Liu, F., Li, R., Zhou, Z., Lin, Z., Song, L., Deng, S., Li, Y., Nong, B., Xia, Y., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00938-z · Cited by 34
mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib
Hanly, E. K., Bednarczyk, R. B., Tuli, N. Y., Moscatello, A. L., Halicka, H. D., Li, J., Geliebter, J., Darżynkiewicz, Z., & Tiwari, R. K. (2015) · Oncotarget · doi:10.18632/oncotarget.4052 · Cited by 33
Analysis of mTOR pathway expression in lymphatic malformation and related diseases
Hori, Y., Ozeki, M., Hirose, K., Matsuoka, K., Matsui, T., Kohara, M., Tahara, S., Toyosawa, S., Fukao, T., & Morii, E. (2020) · Pathology International · doi:10.1111/pin.12913 · Cited by 33
Rapamycin Suppresses Tumor Growth and Alters the Metabolic Phenotype in T-Cell Lymphoma
Kittipongdaja, W., Wu, X., Garner, J. A., Liu, X., Komas, S. M., Hwang, S. T., & Schieke, S. M. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.153 · Cited by 34
Manipulation of endothelial cells by KSHV: Implications for angiogenesis and aberrant vascular differentiation
Ojala, P. M., & Schulz, T. F. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.01.008 · Cited by 33
Treatment of Kaposi Sarcoma-Associated Herpesvirus-Associated Cancers
Dittmer, D. P., Richards, K. L., & Damania, B. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00141 · Cited by 33
Compromised autophagy precedes meniscus degeneration and cartilage damage in mice
Meckes, J. K., Caramés, B., Olmer, M., Kiosses, W. B., Grogan, S. P., Lotz, M. K., & DʼLima, D. D. (2017) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2017.07.023 · Cited by 33
Mammalian target of rapamycin inhibitors in sarcomas
Okuno, S. H. (2006) · Current Opinion in Oncology · doi:10.1097/01.cco.0000228742.72165.cf · Cited by 33
Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study
Guo, J., Huang, Y., Zhang, X., Zhou, F., Sun, Y., Qin, S., Ye, Z., Wang, H., Jappe, A., Straub, P., et al. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-136 · Cited by 32
mTORC signaling in hematopoiesis
Wang, X., Chu, Y., Wang, W., & Yuan, W. (2016) · International Journal of Hematology · doi:10.1007/s12185-016-1944-z · Cited by 32
Systems Biology of Immunomodulation for Post-Stroke Neuroplasticity: Multimodal Implications of Pharmacotherapy and Neurorehabilitation
Alam, M. S., Rallabandi, V. P. S., & Roy, P. K. (2016) · Frontiers in Neurology · doi:10.3389/fneur.2016.00094 · Cited by 33
mTOR Pathway is Involved in Energy Homeostasis Regulation as a Part of the Gut–Brain Axis
Pena-León, V., Pérez-Lois, R., & Seoane, L. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165715 · Cited by 33
Research and innovation in the development of everolimus for oncology
Lebwohl, D., Thomas, G., Lane, H. A., O’Reilly, T., Escudier, B. J., Yao, J. C., Pavel, M., Franz, D. N., Berg, W. J., Baladi, J., et al. (2011) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2011.558079 · Cited by 31
Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade
Cho, J. Y., & Park, J. (2008) · International Journal of Molecular Sciences · doi:10.3390/ijms9112217 · Cited by 32
The mammalian target of rapamycin pathway and its role in molecular nutrition regulation
Lian, J., Yan, X., Peng, J., & Jiang, S. (2008) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200700005 · Cited by 31
The promise of mTOR inhibitors in the treatment of colorectal cancer
Kim, D.-D., & Eng, C. (2012) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2012.721353 · Cited by 31
mTOR signalling: jack-of-all-trades
Hiani, Y. E., Egom, E. E. A., & Dong, X. (2018) · Biochemistry and Cell Biology · doi:10.1139/bcb-2018-0004 · Cited by 30
mTOR Signaling Pathway in Cancer Targets Photodynamic Therapy In Vitro
Ayuk, S. M., & Abrahamse, H. (2019) · Cells · doi:10.3390/cells8050431 · Cited by 30

Authors: Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T.
Affiliations: Mayo Clinic (US)
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author: Abraham, Robert T.
ORCID: Abraham, Robert T.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1995-01
Volume: 270
Issue: 2
Pages: 815-822
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.270.2.815
OpenAlex: W2158612356
Cited by: 887
References: 29
Citations by year: 2026: 10 · 2025: 20 · 2024: 28 · 2023: 37 · 2022: 38 · 2021: 37 · 2020: 39 · 2019: 31 · 2018: 25 · 2017: 38 · 2016: 25 · 2015: 31 · 2014: 26 · 2013: 31 · 2012: 29
FWCI: 9.91
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 9442 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Mayo Foundation for Medical Education and Research
National Institutes of Health
National Institute of General Medical Sciences (R01GM047286, GM47286)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: rapamycin, FKBP12, mTOR, TOR1, TOR2, G1/S transition, T cells, immunosuppressants, rapamycin resistance, YAC-1 cells, cDNA cloning
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, DNA-Binding Proteins, Fungal Proteins, Heat-Shock Proteins, Humans, Molecular Sequence Data, Polyenes, Protein Kinases, Tumor Cells, Cultured, Lymphoma, T-Cell, Rats, Sprague-Dawley, Sequence Homology, Amino Acid, Phosphotransferases (Alcohol Group Acceptor), DNA Primers, DNA, Complementary, Cell Cycle Proteins, Phosphatidylinositol 3-Kinases, Sirolimus, Tacrolimus Binding Proteins, Saccharomyces cerevisiae Proteins, Rats, TOR Serine-Threonine Kinases

About these checks

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks