Guidelines for the use and interpretation of assays for monitoring autophagy
- D. Klionsky, F. Abdalla, Shengzhou or sheng-zhou wu
- BiologyAutophagy
- 1 April 2012
These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
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).
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.
The data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status.
Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling
- T. Ikenoue, K. Inoki, Qian Yang, Xiaoming Zhou, K. Guan
- Biology, ChemistryEMBO Journal
- 23 July 2008
It is shown that the mammalian target of rapamycin complex 2 (mTORC2) has an important function in phosphorylation of both TM and HM in all conventional PKCs, novel PKCε as well as Akt.
Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome.
- M. Corradetti, K. Inoki, N. Bardeesy, R. DePinho, K. Guan
- Biology, MedicineGenes & Development
- 1 July 2004
It is shown that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the Gene mutated in TSC, which suggests that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC 2/mTOR pathway.
Dysregulation of the TSC-mTOR pathway in human disease
- K. Inoki, M. Corradetti, K. Guan
- Biology, MedicineNature Genetics
- 2004
Emerging evidence for a functional relationship between the mTOR signaling pathway and several genetic diseases is discussed, and evidence supporting a model in which dysregulation of mTOR may be a common molecular basis for hamartoma syndromes and for other cellular hypertrophic disorders is presented.
ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
- Angela Alexander, S. Cai, C. Walker
- Biology, MedicineProceedings of the National Academy of Sciences
- 16 February 2010
A cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy is identified, identifying an integration node for the cellular damage response with key pathways involved in metabolism, protein synthesis, and cell survival.
Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes
A distinct cellular compartment at the trans side of the Golgi apparatus, the TOR-autophagy spatial coupling compartment (TASCC), is observed, where (auto)lysosomes and mTOR accumulated during Ras-induced senescence.
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