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Guidelines for the use and interpretation of assays for monitoring autophagy
- D. Klionsky, F. Abdalla, +498 authors Shengzhou or sheng-zhou wu
- Medicine, Biology
- 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. Expand
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed. Expand
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
It is described that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis. Expand
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). Expand
Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control.
It is demonstrated that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway, and YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition. Expand
TEAD mediates YAP-dependent gene induction and growth control.
TEAD is revealed as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP, and is required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. Expand
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. Expand
Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.
2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases, leading to genome-wide histone and DNA methylation alterations. Expand
TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth
Results show that, in addition to transcriptional activation, Wnt stimulates translation and cell growth by activating the TSC-mTOR pathway, and the sequential phosphorylation of TSC2 by AMPK and GSK3 reveals a molecular mechanism of signal integration in cell growth regulation. Expand
Regulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling
This study identifies extracellular diffusible signals that modulate the Hippo pathway and also establishes the hippo-YAP pathway as a critical signaling branch downstream of GPCR. Expand