TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
@article{Inoki2003TSC2MC, title={TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival}, author={Ken Inoki and Tianqing Zhu and Kun Liang Guan}, journal={Cell}, year={2003}, volume={115}, pages={577-590} }
3,639 Citations
Function of p53 in Regulation of TSC Mutant Cell Apoptosis
- Biology
- 2007
The major goal of this proposal is to investigate the functional importance of p53 in energy starvation induced apoptosis in TSC tumor cells and to establish a functional relationship between TSC1/TSC2 and p53 tumor suppressors.
Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1
- BiologyMolecular and Cellular Biology
- 2005
RedD1 is demonstrated to be a critical transducer of the cellular response to energy depletion through the TSC-mTOR pathway.
TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth
- BiologyCell
- 2006
Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway
- BiologyCell cycle
- 2005
The finding that REDD 1-dependent TOR regulation contributes to cell growth/cell size control in flies and mammals suggests that abnormalities of REDD1-mediated signaling might disrupt energy homeostasis and/or promote tumorigenesis.
The TSC1-TSC2 complex: a molecular switchboard controlling cell growth.
- BiologyThe Biochemical journal
- 2008
The present review focuses on the molecular details of TSC1-TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1.
TSC1-TSC2 complex on the crossroad of pancreatic β cell signaling. Role on cell proliferation, death and survival
- Biology
- 2010
It is found that either insulin, glucose independent signaling or the energetic status of the cell are able to modulate TSC2 phosphorylation in pancreatic β cell lines and specific expression of insulin receptor isoform A restored insulin signalling under these conditions.
AMPK phosphorylation of raptor mediates a metabolic checkpoint.
- Biology, ChemistryMolecular cell
- 2008
GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress.
- BiologyInternational journal of molecular medicine
- 2007
It is demonstrated that crosstalk between GADD34 and the mTOR signaling pathways contributes to the response of the protein synthetic machinery to environmental stress and may find clinical potential as a target drug for the treatment of mTOR-associated diseases.
The coordinate regulation of the p53 and mTOR pathways in cells.
- BiologyProceedings of the National Academy of Sciences of the United States of America
- 2005
The results presented here demonstrate that activation of p53 inhibits mTOR activity and regulates its downstream targets, including autophagy, a tumor suppression process, and that p53 and mTOR signaling machineries can cross-talk and coordinately regulate cell growth, proliferation, and death.
References
SHOWING 1-10 OF 53 REFERENCES
Tsc tumour suppressor proteins antagonize amino-acid–TOR signalling
- BiologyNature Cell Biology
- 2002
These studies identify Tsc1 and Tsc2 as regulators of the amino acid–TOR pathway and provide a new paradigm for how proteins involved in nutrient sensing function as tumour suppressors.
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
- BiologyNature Cell Biology
- 2002
It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR).
Akt regulates growth by directly phosphorylating Tsc2
- Biology, Computer ScienceNature Cell Biology
- 2002
Drosophila melanogaster Tsc2 seems to be the critical target of Akt in mediating growth signals for the insulin signalling pathway, and Stimulating Akt/PKB signalling in vivo markedly increases cell growth/size, disrupts the Tsc1–Tsc2 complex and disturbs the distinct subcellular localization of T Sc2.
Drosophila Tsc1 Functions with Tsc2 to Antagonize Insulin Signaling in Regulating Cell Growth, Cell Proliferation, and Organ Size
- BiologyCell
- 2001
Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors.
- Biology, MedicineCancer research
- 2002
In the Eker rat, short-term inhibition of mTOR by rapamycin was associated with a significant tumor response, including induction of apoptosis and reduction in cell proliferation, and these changes were not accompanied by significant alteration in cyclin D1 and p27 levels.
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E.
- BiologyGenes & development
- 2002
Data show that mTOR signals downstream to at least two independent targets, S6K1 and 4EBP1/eIF4E, that function in translational control to regulate mammalian cell size.
Phosphatidylinositol 3-Kinase/Akt Pathway Regulates Tuberous Sclerosis Tumor Suppressor Complex by Phosphorylation of Tuberin*
- Biology, ChemistryThe Journal of Biological Chemistry
- 2002
It is shown that insulin or insulin growth factor (IGF) 1 stimulates phosphorylation of tuberin, which is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 but not by the mitogen-activated protein kinase inhibitor PD98059, and that phosphorylated by PI3K/Akt is a major mechanism controlling hamartin-tuberin function.
Tuberin Regulates p70 S6 Kinase Activation and Ribosomal Protein S6 Phosphorylation
- BiologyThe Journal of Biological Chemistry
- 2002
It is found that ribosomal protein S6 (S6), which exerts translational control of protein synthesis and is required for cell growth, is hyperphosphorylated in the smooth muscle-like cell lesions of LAM patients compared with smooth muscle cells from normal human blood vessels and trachea.
AMP‐activated protein kinase: the energy charge hypothesis revisited
- BiologyBioEssays : news and reviews in molecular, cellular and developmental biology
- 2001
The AMP‐activated protein kinase cascade is a sensor of cellular energy charge, and its existence provides strong support for the energy charge hypothesis first proposed by Daniel Atkinson in the…
Regulation of mammalian translation factors by nutrients.
- BiologyEuropean journal of biochemistry
- 2002
Data indicate the operation of additional, and so far unknown, regulatory mechanisms that control eIF2B activity, which controls the recruitment of the initiator methionyl-tRNA to the ribosome and is activated by insulin in the absence of glucose or amino acids.