PreprintCited by 710PI3K/AKT/mTOR signaling in cancerCancer, Hypoxia, and MetabolismTuberous Sclerosis Complex Research

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.

Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling

Open access

DeYoung, Maurice Phillip, Horak, Peter, Sofer, Avi, Sgroi, Dennis, Ellisen, Leif W.·2008·Genes & Development

DOI 10.1101/gad.1617608PMC PMC2192757

Open this paper in CoChat — free account Open PDF

Abstract

Hypoxia induces rapid and dramatic changes in cellular metabolism, in part through inhibition of target of rapamycin (TOR) kinase complex 1 (TORC1) activity. Genetic studies have shown the tuberous sclerosis tumor suppressors TSC1/2 and the REDD1 protein to be essential for hypoxia regulation of TORC1 activity in Drosophila and in mammalian cells. The molecular mechanism and physiologic significance of this effect of hypoxia remain unknown. Here, we demonstrate that hypoxia and REDD1 suppress mammalian TORC1 (mTORC1) activity by releasing TSC2 from its growth factor-induced association with inhibitory 14–3–3 proteins. Endogenous REDD1 is required for both dissociation of endogenous TSC2/14–3–3 and inhibition of mTORC1 in response to hypoxia. REDD1 mutants that fail to bind 14–3–3 are defective in eliciting TSC2/14–3–3 dissociation and mTORC1 inhibition, while TSC2 mutants that do not bind 14-3-3 are inactive in hypoxia signaling to mTORC1. In vitro, loss of REDD1 signaling promotes proliferation and anchorage-independent growth under hypoxia through mTORC1 dysregulation. In vivo, REDD1 loss elicits tumorigenesis in a mouse model, and down-regulation of REDD1 is observed in a subset of human cancers. Together, these findings define a molecular mechanism of signal integration by TSC1/2 that provides insight into the ability of REDD1 to function in a hypoxia-dependent tumor suppressor pathway.

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 · 10.1101/gad.1617608

Cites

42 of 42 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.

Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
Defining the role of mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K., Li, Y., Xu, T., & Guan, K.-L. (2003) · Genes & Development · doi:10.1101/gad.1110003 · Cited by 1,911
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
The Tuberous Sclerosis Complex
Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmra055323 · Cited by 1,793
Growing roles for the mTOR pathway
Sarbassov, D. D., Ali, S. M., & Sabatini, D. M. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.009 · Cited by 1,590
Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., & Cantley, L. C. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00568-3 · Cited by 1,555
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384
Self-citation
Gene expression profiling identifies clinically relevant subtypes of prostate cancer
Lapointe, J., Li, C., Higgins, J., van de Rijn, M., Bair, E., Montgomery, K. D., Ferrari, M. K., Egevad, L., Rayford, W., Bergerheim, U. S. R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0304146101 · Cited by 1,282

Show all 41 references

Sorted by citations

Items 301–400 of 710

Probing the GTPase cycle with real-time NMR: GAP and GEF activities in cell extracts
Marshall, C. B., Meiri, D., Smith, M. J., Mazhab-Jafari, M. T., Gasmi-Seabrook, G. M. C., Rottapel, R., Stambolic, V., & Ikura, M. (2012) · Methods · doi:10.1016/j.ymeth.2012.06.014 · Cited by 46
Translational control by oncogenic signaling pathways
Gao, B., & Roux, P. P. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.11.006 · Cited by 46
Autoinflammation: Lessons from the study of familial Mediterranean fever
Skendros, P., Papagoras, C., Mitroulis, I., & Ritis, K. (2019) · Journal of Autoimmunity · doi:10.1016/j.jaut.2019.102305 · Cited by 45
Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation
XU, M.-C., Shi, H., Wang, H., & Gao, X. (2013) · Molecular Medicine Reports · doi:10.3892/mmr.2013.1468 · Cited by 45
Rapid induction of REDD1 expression by endurance exercise in rat skeletal muscle
Murakami, T., Hasegawa, K., & Yoshinaga, M. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.01.078 · Cited by 48
Dampened VEPH1 activates mTORC1 signaling by weakening the TSC1/TSC2 association in hepatocellular carcinoma
Dong, P., Wang, X., Liu, L., Tang, W., Ma, L., Zeng, W., Sun, S., Zhang, L., Zhang, N., Shen, X., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.06.027 · Cited by 45
Cellular adaptation to nutrient deprivation: crosstalk between the mTORC1 and eIF2α signaling pathways and implications for autophagy
Wengrod, J., & Gardner, L. B. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1056947 · Cited by 46
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
Survival by self-destruction: A role for autophagy in the placenta?
Bildirici, İ., Longtine, M. S., Chen, B., & Nelson, D. M. (2012) · Placenta · doi:10.1016/j.placenta.2012.04.011 · Cited by 44
Multifaceted Role of Insulin-Like Growth Factors and Mammalian Target of Rapamycin in Skeletal Muscle
Frost, R. A., & Lang, C. H. (2012) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2012.04.012 · Cited by 47
Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes
Kalam, F., James, D. L., Li, Y. R., Coleman, M. F., Kiesel, V. A., Feliciano, E. M. C., Hursting, S. D., Sears, D. D., & Kleckner, A. S. (2023) · JNCI Monographs · doi:10.1093/jncimonographs/lgad008 · Cited by 49
The mTOR Signaling Pathway Interacts with the ER Stress Response and the Unfolded Protein Response in Cancer
Mafi, S., Ahmadi, E., Meehan, E. V., Chiari, C. C., Mansoori, B., Sadeghi, H., Milani, S., Jafarinia, M., Taeb, S., Bashmagh, B. M., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-3032 · Cited by 43
Impaired hypertrophy in myoblasts is improved with testosterone administration
Deane, C. S., Hughes, D. C., Sculthorpe, N. F., Lewis, M. P., Stewart, C. E., & Sharples, A. P. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.05.005 · Cited by 43
Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model
Chaillou, T., Koulmann, N., Simler, N., Meunier, A., Serrurier, B., Chapot, R., Peinnequin, A., Beaudry, M., & Bigard, X. A. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00262.2011 · Cited by 45
PI3K inhibitors protect against glucocorticoid-induced skin atrophy
Agarwal, S., Mirzoeva, S., Readhead, B., Dudley, J. T., & Budunova, I. V. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.055 · Cited by 42
Kinase mTOR: Regulation and role in maintenance of cellular homeostasis, tumor development, and aging
Parkhitko, A. A., Favorova, O. O., Khabibullin, D., Anisimov, V. N., & Henske, E. P. (2014) · Biochemistry (Moscow) · doi:10.1134/s0006297914020023 · Cited by 44
Inhibition of mTOR kinase as a therapeutic target for acute myeloid leukemia
Tabe, Y., Tafuri, A., Sekihara, K., Yang, H., & Konopleva, M. Y. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1333600 · Cited by 44
Induction of HSP27 and HSP70 by constitutive overexpression of Redd1 confers resistance of lung cancer cells to ionizing radiation
Jin, H., Hong, S., Kim, J., Kim, M., Chang, Y. H., Hong, Y. J., Lee, J., & Park, I. (2019) · Oncology Reports · doi:10.3892/or.2019.7036 · Cited by 42
mTOR-Mediated Antioxidant Activation in Solid Tumor Radioresistance
Woo, Y., Lee, H.-J., Jung, Y. M., & Jung, Y. (2019) · Journal of Oncology · doi:10.1155/2019/5956867 · Cited by 42
Regulation of REDD1 by insulin‐like growth factor‐I in skeletal muscle and myotubes
Frost, R. A., Huber, D. S., Pruznak, A. M., & Lang, C. H. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22349 · Cited by 42
p53-mediated AKT and mTOR inhibition requires RFX7 and DDIT4 and depends on nutrient abundance
Coronel, L., Häckes, D., Schwab, K., Riege, K., Hoffmann, S., & Fischer, M. (2021) · Oncogene · doi:10.1038/s41388-021-02147-z · Cited by 40
mTOR inhibitors in targeting autophagy and autophagy-associated signaling for cancer cell death and therapy
Senapati, P. K., Mahapatra, K. K., Singh, A., & Bhutia, S. K. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189342 · Cited by 44
Clinical activity of mammalian target of rapamycin inhibitors in solid tumors
Alvarado, Y., Mita, M. M., Vemulapalli, S., Mahalingam, D., & Mita, A. C. (2011) · Targeted Oncology · doi:10.1007/s11523-011-0178-5 · Cited by 41
Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life
Pallavi, R., Giorgio, M., & Pelicci, P. G. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00318 · Cited by 40
Myoblast models of skeletal muscle hypertrophy and atrophy
Sharples, A. P., & Stewart, C. E. (2011) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e3283457ade · Cited by 43
Dysregulation of mTOR Signaling after Brain Ischemia
Villa-González, M., Martín-López, G., & Pérez-Álvarez, M. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052814 · Cited by 41
REDD1 (regulated in development and DNA damage response 1) expression in skeletal muscle as a surrogate biomarker of the efficiency of glucocorticoid receptor blockade
Kumari, R., Willing, L. B., Jefferson, L. S., Simpson, I. A., & Kimball, S. R. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.08.017 · Cited by 40
Inhibition of Polo-like Kinase 1 (Plk1) Enhances the Antineoplastic Activity of Metformin in Prostate Cancer
Shao, C., Ahmad, N., Hodges, K. B., Kuang, S., Ratliff, T., & Liu, X. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.596817 · Cited by 42
Hair curvature: a natural dialectic and review
Nissimov, J., & Chaudhuri, A. B. D. (2014) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12081 · Cited by 40
Hypoxia and muscle maintenance regulation
de Theije, C. C., Costes, F., LANGEN, R. C. J., Pison, C. M., & Gosker, H. R. (2011) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32834b6e79 · Cited by 41
siRNA-Mediated Knockdown of the mTOR Inhibitor RTP801 Promotes Retinal Ganglion Cell Survival and Axon Elongation by Direct and Indirect Mechanisms
Morgan-Warren, P. J., O'Neill, J., de Cogan, F., Spivak, I., Ashush, H., Kalinski, H., Ahmed, Z., Berry, M., Feinstein, E., Scott, R. A. H., et al. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-17511 · Cited by 40
Autophagic Mechanism in Anti-Cancer Immunity: Its Pros and Cons for Cancer Therapy
Li, Y.-Y., Feun, L. G., Thongkum, A., Tu, C.-H., Chen, S.-M., Wangpaichitr, M., Wu, C., Kuo, M. T., & Savaraj, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061297 · Cited by 40
Iron chelation inhibits mTORC1 signaling involving activation of AMPK and REDD1/Bnip3 pathways
Shang, C., Zhou, H., Liu, W., Shen, T., Luo, Y., & Huang, S. (2020) · Oncogene · doi:10.1038/s41388-020-1366-5 · Cited by 43
Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1
Kim, T. S., Lee, M., Park, M., Kim, S. Y., Shim, M. S., Lee, C. Y., Choi, D. H., & Cho, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221810027 · Cited by 40
mTOR Signaling Pathway and Gut Microbiota in Various Disorders: Mechanisms and Potential Drugs in Pharmacotherapy
Gao, Y., & Tian, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411811 · Cited by 39
TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1
Plescher, M., Teleman, A. A., & Demetriades, C. (2015) · Scientific Reports · doi:10.1038/srep13828 · Cited by 36
Metformin: An Inhibitor of mTORC1 Signaling
Melnik, B. C., & Schmitz, G. (2014) · Cited by 39
The effect of rapamycin treatment on cerebral ischemia: A systematic review and meta-analysis of animal model studies
Beard, D. J., Hadley, G., Thurley, N., Howells, D., Sutherland, B. A., & Buchan, A. (2018) · International Journal of Stroke · doi:10.1177/1747493018816503 · Cited by 34
Chrysanthemum zawadskil Herbich attenuates dexamethasone-induced muscle atrophy through the regulation of proteostasis and mitochondrial function
Lee, H., Kim, Y. I., Nirmala, F. S., Jeong, H. Y., Seo, H., Ha, T. Y., Jung, C. H., & Ahn, J. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111226 · Cited by 40
High expression of DNA damage-inducible transcript 4 (DDIT4) is associated with advanced pathological features in the patients with colorectal cancer
Fattahi, F., Zanjani, L. S., Shams, Z. H., Kiani, J., Mehrazma, M., Najafi, M., & Madjd, Z. (2021) · Scientific Reports · doi:10.1038/s41598-021-92720-z · Cited by 41
Differential redox proteomics allows identification of proteins reversibly oxidized at cysteine residues in endothelial cells in response to acute hypoxia
Izquierdo-Álvarez, A., Ramos, E. M., Villanueva, J., Hernansanz‐Agustín, P., Fernández‐Rodríguez, R., Tello, D., Carrascal, M., & Martı́nez-Ruiz, A. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.06.035 · Cited by 38
Aberrant REDD1-mTORC1 responses to insulin in skeletal muscle from Type 2 diabetics
Williamson, D. L., Dungan, C. M., Mahmoud, A. M., Mey, J. T., Blackburn, B. K., & Haus, J. M. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00285.2015 · Cited by 45
Responses of Skeletal Muscle Hypertrophy in Wistar Rats to Different Resistance Exercise Models
Luciano, T. F., Marques, S. D. O., Pieri, B. L. D. S., de Souza, D. R., ARAÚJO, L. V., Nesi, R. T., Scheffer, D. D. L., Comin, V. H., Pinho, R. A., Muller, A. P., et al. (2017) · Physiological Research · doi:10.33549/physiolres.933256 · Cited by 38
Autophagy: Mechanisms, regulation, and its role in tumorigenesis
Parkhitko, A. A., Favorova, O. O., & Henske, E. P. (2013) · Biochemistry (Moscow) · doi:10.1134/s0006297913040044 · Cited by 39
Human skeletal muscle wasting in hypoxia: a matter of hypoxic dose?
D’Hulst, G., & Deldicque, L. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00264.2016 · Cited by 38
Overexpression of the recently identified oncogene REDD1 correlates with tumor progression and is an independent unfavorable prognostic factor for ovarian carcinoma
Chang, B., Meng, J., Zhu, H., Du, X., Sun, L., Wang, L., Li, S., & Yang, G. S. (2018) · Diagnostic Pathology · doi:10.1186/s13000-018-0754-4 · Cited by 37
Translating the Hypoxic Response—The Role of HIF Protein Translation in the Cellular Response to Low Oxygen
Ivanova, I. G., Park, C. V., & Kenneth, N. S. (2019) · Cells · doi:10.3390/cells8020114 · Cited by 39
Histone Deacetylase 6 (HDAC6) Promotes the Pro-survival Activity of 14-3-3ζ via Deacetylation of Lysines within the 14-3-3ζ Binding Pocket
Mortenson, J. B., Heppler, L. N., Banks, C. J., Weerasekara, V. K., Whited, M. D., Piccolo, S., Johnson, W. E., Thompson, J. W., & Andersen, J. L. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.607580 · Cited by 36
ATM Protein Kinase Signaling, Type 2 Diabetes and Cardiovascular Disease
Espach, Y., Lochner, A., Strijdom, H., & Huisamen, B. (2015) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-015-6571-z · Cited by 35
REDD1 and p-AKT over-expression may predict poor prognosis in ovarian cancer.
Jia, W., Chang, B., Sun, L., Zhu, H., Pang, L., Lin, T., Zou, H., Du, J.-Z., Dong, Y., Yan, Q., et al. (2014) · PubMed Central · Cited by 36
Profiling the molecular mechanism of fullerene cytotoxicity on tumor cells by RNA-seq
Lucafò, M., Gerdol, M., Pallavicini, A., Pacor, S., Zorzet, S., Ros, T. D., Prato, M., & Sava, G. (2013) · Toxicology · doi:10.1016/j.tox.2013.10.001 · Cited by 34
Plasma membrane translocation of REDD1 governed by GPCRs contributes to mTORC1 activation
Michel, G., Matthes, H. W. D., Hachet‐Haas, M., Baghdadi, K. E., Mey, J. D., Pepperkok, R., Simpson, J. C., Galzi, J., & Lecat, S. (2013) · Journal of Cell Science · doi:10.1242/jcs.136432 · Cited by 36
A central role for hypoxia-inducible factor (HIF)-2α in hepatic glucose homeostasis
Ramakrishnan, S. K., & Shah, Y. M. (2017) · Nutrition and Healthy Aging · doi:10.3233/nha-170022 · Cited by 37
Role of the HIF oxygen sensing pathway in cell defense and proliferation through the control of amino acid metabolism
Bouthelier, A., & Aragonés, J. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118733 · Cited by 37
Loss of REDD1 prevents chemotherapy‐induced muscle atrophy and weakness in mice
Hain, B. A., Xu, H., & Waning, D. L. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12795 · Cited by 36
Hypoxia as a target for drug combination therapy of liver cancer
Bowyer, C. J., Lewis, A. L., Lloyd, A. W., Phillips, G. J., & Macfarlane, W. M. (2017) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000516 · Cited by 35
TGFβ-Induced Deptor Suppression Recruits mTORC1 and Not mTORC2 to Enhance Collagen I (α2) Gene Expression
Das, F., Bera, A., Ghosh‐Choudhury, N., Abboud, H. E., Kasinath, B. S., & Choudhury, G. G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109608 · Cited by 37
SP600125 negatively regulates the mammalian target of rapamycin via ATF4‐induced Redd1 expression
Jin, H.-O., Seo, S.-K., Woo, S., Kim, E.-S., Lee, H.-C., Yoo, D.-H., Choe, T.-B., Hong, S.-I., Kim, J.-I., & Park, I. (2009) · FEBS Letters · doi:10.1016/j.febslet.2008.11.035 · Cited by 39
RES-529
Weinberg, M. A. (2016) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000354 · Cited by 36
MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies
Sionov, R. V. (2013) · ISRN Hematology · doi:10.1155/2013/348212 · Cited by 35
Induction of REDD1 via AP-1 prevents oxidative stress-mediated injury in hepatocytes
Cho, S. S., Kim, K. M., Yang, J. H., ‍Kim, D. Y., Park, S. J., Kim, S. J., Kim, J. K., Cho, I. J., & Ki, S. H. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.06.014 · Cited by 37
The stress response protein REDD1 as a causal factor for oxidative stress in diabetic retinopathy
Miller, W. P., Sunilkumar, S., & Dennis, M. D. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.01.041 · Cited by 35
Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2
Morel, M., Couturier, J., Pontcharraud, R., Gil, R., Fauconneau, B., Paccalin, M., & Page, G. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.07.004 · Cited by 36
Furthering the design and the discovery of small molecule ATP-competitive mTOR inhibitors as an effective cancer treatment
Lv, X., Ma, X., & Hu, Y. (2013) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2013.800479 · Cited by 34
Targeting carbonic anhydrase IX improves the anti-cancer efficacy of mTOR inhibitors
Faes, S., Planche, A., Uldry, É., Santoro, T., Pythoud, C., Stehle, J., Horlbeck, J., Letovanec, I., Riggi, N., Datta, D. B., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9134 · Cited by 33
Muscle Protein Turnover and the Molecular Regulation of Muscle Mass during Hypoxia
Pasiakos, S. M., Berryman, C. E., Carrigan, C. T., Young, A., & Carbone, J. W. (2017) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001228 · Cited by 36
Deciphering the Molecular Mechanisms Sustaining the Estrogenic Activity of the Two Major Dietary Compounds Zearalenone and Apigenin in ER-Positive Breast Cancer Cell Lines
Lecomte, S., Demay, F., Pham, T. H., Moulis, S., Efstathiou, T., Chalmel, F., & Pakdel, F. (2019) · Nutrients · doi:10.3390/nu11020237 · Cited by 35
Autophagy as a Stress Response Pathway in the Immune System
Bhattacharya, A., & Eissa, N. T. (2015) · International Reviews of Immunology · doi:10.3109/08830185.2014.999156 · Cited by 37
DDIT4 regulates mesenchymal stem cell fate by mediating between HIF1α and mTOR signalling
Gharibi, B., Ghuman, M. S., & Hughes, F. J. (2016) · Scientific Reports · doi:10.1038/srep36889 · Cited by 35
Glucocorticoid Receptor Signaling Impairs Protein Turnover Regulation in Hypoxia-Induced Muscle Atrophy in Male Mice
de Theije, C. C., Schols, A. M. W. J., Lamers, W. H., Ceelen, J., van Gorp, R. H., Hermans, J. J. R., Köhler, E. S., & LANGEN, R. C. J. (2017) · Endocrinology · doi:10.1210/en.2017-00603 · Cited by 33
Mutant p53 induces a hypoxia transcriptional program in gastric and esophageal adenocarcinoma
Sethi, N. S., Kikuchi, O., McFarland, J. M., Zhang, Y., Chung, M., Kafker, N., Islam, M., Lampson, B. L., Chakraborty, A. A., Kaelin, W. G., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.128439 · Cited by 35
Transcriptome profiling of tiger pufferfish (Takifugu rubripes) gills in response to acute hypoxia
Shang, F., Bao, M., Liu, F., Hu, Z., Wang, S., Yang, X., Yu, Y., Zhang, H., Jiang, C., Qiu, X., et al. (2022) · Aquaculture · doi:10.1016/j.aquaculture.2022.738324 · Cited by 33
REDD1 induction regulates the skeletal muscle gene expression signature following acute aerobic exercise
Gordon, B. S., Steiner, J. L., Rossetti, M. L., Qiao, S., Ellisen, L. W., Govindarajan, S. S., Eroshkin, A. M., Williamson, D. L., & Coen, P. M. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00120.2017 · Cited by 33
Self-citation
Consequences of irradiation on adult spermatogenesis: Between infertility and hereditary risk
Marjault, H., & Allemand, I. (2016) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2016.07.004 · Cited by 32
Role of Akt-independent mTORC1 and GSK3β signaling in sublethal NMDA-induced injury and the recovery of neuronal electrophysiology and survival
Swiatkowski, P., Nikolaeva, I., Kumar, G., Zucco, A. J., Akum, B. F., Patel, M. V., D’Arcangelo, G., & Firestein, B. L. (2017) · Scientific Reports · doi:10.1038/s41598-017-01826-w · Cited by 33
The functional significance of 14-3-3 proteins in cancer: focus on lung cancer
Khorrami, A., Bagheri, M. S., Tavallaei, M., & Gharechahi, J. (2017) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2017-0032 · Cited by 32
Extracellular vesicles degradation pathway based autophagy lysosome pathway.
Zheng, J., Tan, J., Miao, Y., & Zhang, Q. (2019) · Europe PMC (PubMed Central) · Cited by 32
REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-κB activation
Lee, D., Kim, T., Byeon, J., Park, M., Kim, S., Kim, J., Choi, S., Lee, G., Park, C., Lee, K. W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34110-1 · Cited by 35
Loss of Hepatocyte-Nuclear-Factor-1α Impacts on Adult Mouse Intestinal Epithelial Cell Growth and Cell Lineages Differentiation
Lussier, C. R., Brial, F., Roy, S. A. B., Langlois, M., Verdu, E. F., Rivard, N., Perreault, N., & Boudreau, F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012378 · Cited by 33
The role of oxidized ATM in the regulation of oxidative stress-induced energy metabolism reprogramming of CAFs
Tang, S., Yang, L., Tang, X., & Liu, M. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.07.028 · Cited by 33
The Stress-Response Gene redd1 Regulates Dorsoventral Patterning by Antagonizing Wnt/β-catenin Activity in Zebrafish
Feng, Q., Zou, X., Lu, L., Li, Y., Liu, Y., Zhou, J., & Duan, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052674 · Cited by 31
Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone-Induced Muscle Atrophy In Vitro
Tsuchida, W., Iwata, M., Akimoto, T., Matsuo, S., Asai, Y., & Suzuki, S. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25609 · Cited by 31
Alcoholic Cardiomyopathy: Disrupted Protein Balance and Impaired Cardiomyocyte Contractility
Steiner, J. L., & Lang, C. H. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13405 · Cited by 34
REDD1 Is Essential for Optimal T Cell Proliferation and Survival
Reuschel, E. L., Wang, J., Shivers, D. K., Muthumani, K., Weiner, D. B., Ma, Z., & Finkel, T. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0136323 · Cited by 31
Dysregulated mTORC1-Dependent Translational Control: From Brain Disorders to Psychoactive Drugs
Santini, E., & Klann, E. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00076 · Cited by 34
Grow₂: the HIF system, energy homeostasis and the cell cycle.
Moniz, S., Biddlestone, J., & Rocha, S. (2014) · PubMed · doi:10.14670/hh-29.10.589 · Cited by 30
von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology
Shirole, N. H., & Kaelin, W. G. (2023) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2023.04.011 · Cited by 34
Advances in understanding the mechanisms of evasive and innate resistance to mTOR inhibition in cancer cells
Chiarini, F., Evangelisti, C., Lattanzi, G., McCubrey, J. A., & Martelli, A. M. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.03.013 · Cited by 32
The RAL signaling network: Cancer and beyond
Apken, L. H., & Oeckinghaus, A. (2020) · International review of cytology · doi:10.1016/bs.ircmb.2020.10.005 · Cited by 30
Glyceollins trigger anti-proliferative effects through estradiol-dependent and independent pathways in breast cancer cells
Lecomte, S., Chalmel, F., Ferrière, F., Percevault, F., Plu, N., Saligaut, C., Surel, C., Lelong, M., Efstathiou, T., & Pakdel, F. (2017) · Cell Communication and Signaling · doi:10.1186/s12964-017-0182-1 · Cited by 30
NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets
Indini, A., Fiorilla, I., Ponzone, L., Calautti, E., & Audrito, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179985 · Cited by 31
Recent Development in Targeting PI3K-Akt-mTOR Signaling for Anticancer Therapeutic Strategies
Qazi, A. K., Hussain, A., Hamid, A., Qurishi, Y., Majeed, R., Ahmad, M., Najar, R. A., Bhat, J. A., Singh, S. K., Zargar, M. A., et al. (2013) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520613666131125123241 · Cited by 29
Rtp801 Suppression of Epithelial mTORC1 Augments Endotoxin-Induced Lung Inflammation
Nadon, A. M., Perez, M. J., Hernández-Saavedra, D., Smith, L. P., Yang, Y., Sanders, L., Gandjeva, A., Chabon, J. J., Koyanagi, D. E., Graham, B. B., et al. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.06.002 · Cited by 29
REDD1/DDIT4-Independent mTORC1 Inhibition and Apoptosis by Glucocorticoids in Thymocytes
Wolff, N. C., McKay, R. M., & Brugarolas, J. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0625 · Cited by 30
Hypoxia impairs adaptation of skeletal muscle protein turnover- and AMPK signaling during fasting-induced muscle atrophy
de Theije, C. C., Schols, A. M. W. J., Lamers, W. H., Neumann, D., Köhler, E., & LANGEN, R. C. J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203630 · Cited by 30
The SCL/TAL1 Transcription Factor Represses the Stress Protein DDiT4/REDD1 in Human Hematopoietic Stem/Progenitor Cells
Benyoucef, A., Calvo, J., Renou, L., Arcangeli, M.-L., van den Heuvel, A., Amsellem, S., Mehrpour, M., Larghero, J., Soler, É., Naguibneva, I., et al. (2015) · Stem Cells · doi:10.1002/stem.2028 · Cited by 31
miR-181a Participates in Contextual Fear Memory Formation Via Activating mTOR Signaling Pathway
Xu, X., Jing, X., Ma, H., Yuan, R.-R., Dong, Q., Dong, J., Han, X., Chen, Z.-Y., Li, X., & Wang, Y. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx201 · Cited by 29
Druggable Biochemical Pathways and Potential Therapeutic Alternatives to Target Leukemic Stem Cells and Eliminate the Residual Disease in Chronic Myeloid Leukemia
Muselli, F., Peyron, J., & Mary, D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225616 · Cited by 28
Rapamycin Induces an eNOS (Endothelial Nitric Oxide Synthase) Dependent Increase in Brain Collateral Perfusion in Wistar and Spontaneously Hypertensive Rats
Beard, D. J., Li, Z., Schneider, A. M., Couch, Y., Cipolla, M. J., & Buchan, A. M. (2020) · Stroke · doi:10.1161/strokeaha.120.029781 · Cited by 27
Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125
Caporali, S., Alvino, E., Levati, L., Esposito, A. I., Ciomei, M., Brasca, M. G., Bufalo, D. D., Desideri, M., Bonmassar, E., Pfeffer, U., et al. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.06.004 · Cited by 27

Authors: DeYoung, M. P., Horak, P., Sofer, A., Sgroi, D., & Ellisen, L. W.
Affiliations: Harvard University (US)
ORCID: DeYoung, Maurice Phillip
Horak, Peter
Sgroi, Dennis
Ellisen, Leif W.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2008-01-15
Volume: 22
Issue: 2
Pages: 239-251
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.1617608
PMC: PMC2192757
OpenAlex: W2130396048
Cited by: 710
References: 41
Citations by year: 2026: 24 · 2025: 26 · 2024: 17 · 2023: 32 · 2022: 37 · 2021: 43 · 2020: 34 · 2019: 38 · 2018: 41 · 2017: 42 · 2016: 44 · 2015: 42 · 2014: 48 · 2013: 45 · 2012: 47
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA122589)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Genetics (clinical) › Tuberous Sclerosis Complex Research
Keywords: hypoxia, TSC1/2, mTORC1, REDD1, 14-3-3 proteins, TORC1 inhibition, tumor suppression, anchorage-independent growth, carcinogenesis, cellular metabolism, signal integration
MeSH terms: Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Animals, Breast Neoplasms, Cells, Cultured, Humans, Mice, Nude, Models, Biological, Neoplasm Transplantation, Protein Kinases, Transcription Factors, Signal Transduction, Cell Hypoxia, Tumor Suppressor Proteins, Mice, 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

Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling

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