The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The Stress-inducted Proteins RTP801 and RTP801L Are Negative Regulators of the Mammalian Target of Rapamycin Pathway
Open accessAbstract
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays an essential role in cell growth control. mTOR stimulates cell growth by phosphorylating p70 ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding protein 1 (4EBP1). The mTOR pathway is regulated by a wide variety of cellular signals, including mitogenic growth factors, nutrients, cellular energy levels, and stress conditions. Recent studies have proposed several mechanisms to explain how mTOR is regulated by growth factors and cellular energy levels. However, little is known as to how mTOR is regulated by stress conditions. We observed that two stress-induced proteins, RTP801/Redd1 and RTP801L/Redd2, potently inhibit signaling through mTOR. Our data support that RTP801 and RTP801L work downstream of AKT and upstream of TSC2 to inhibit mTOR functions. These results add a new dimension to mTOR pathway regulation and provide a possible molecular mechanism of how cellular stress conditions may regulate mTOR function.
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“Redd1 is a new stress-induced protein and is known as a negative regulator of mTOR through TSC1/TSC2 complex [106–115].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [109]
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Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
Self-citationTSC2 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
Self-citationRheb 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
Self-citationManning, 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
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
Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,264
The AMP-activated protein kinase pathway – new players upstream and downstream
Hardie, D. G. (2004) · Journal of Cell Science · doi:10.1242/jcs.01540 · Cited by 1,163
Dysregulation of the TSC-mTOR pathway in human disease
Inoki, K., Corradetti, M. N., & Guan, K. (2004) · Nature Genetics · doi:10.1038/ng1494 · Cited by 980
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Research works printed but not linked: 1
- Monfar, 1996, Mol. Endocrinol., 10, 1107
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Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR Pathway
Park, K. K., Liu, K., Hu, Y., Smith, P. D., Wang, C., Cai, B., Xu, B., Connolly, L., Kramvis, I., Sahin, M., et al. (2008) · Science · doi:10.1126/science.1161566 · Cited by 1,686
PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase
Sancak, Y., Thoreen, C. C., Peterson, T. R., Lindquist, R. A., Kang, S. A., Spooner, E., Carr, S. A., & Sabatini, D. M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.003 · Cited by 1,236
DeYoung, M. P., Horak, P., Sofer, A., Sgroi, D., & Ellisen, L. W. (2008) · Genes & Development · doi:10.1101/gad.1617608 · Cited by 710
Hypoxia-induced energy stress regulates mRNA translation and cell growth
Liu, L., Cash, T. P., Jones, R. G., Keith, B., Thompson, C. B., & Simon, M. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.010 · Cited by 607
Morrison, D. K. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.10.003 · Cited by 609
Metadata
- Authors
- Corradetti, M. N., Inoki, K., & Guan, K.-L.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Guan, Kun-Liang
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 280
- Issue
- 11
- Pages
- 9769-9772
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2093341871
- Cited by
- 237
- References
- 37
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 9 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 11 · 2015: 18 · 2014: 17 · 2013: 14 · 2012: 16
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5-T32-HD075005)
- 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 › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mTOR signaling, RTP801, REDD1, stress proteins, Akt, TSC2, p70 S6 kinase, 4E-BP1, cell growth regulation, cellular stress
- MeSH terms
- Animals, Hypoxia, Cell Line, DNA Damage, DNA-Binding Proteins, Gene Expression Regulation, Glucocorticoids, Humans, Models, Biological, Phosphorylation, Protein Kinases, Proteins, Retroviridae, Transcription Factors, Transfection, Protein Biosynthesis, RNA Interference, RNA, Small Interfering, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Mice, TOR Serine-Threonine Kinases
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