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Guidelines for the use and interpretation of assays for monitoring autophagy
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
Cell cycle checkpoint signaling through the ATM and ATR kinases.
  • R. Abraham
  • Biology, Medicine
  • Genes & development
  • 1 September 2001
These checkpoints contain, as their most proximal signaling elements, sensor proteins that scan chromatin for partially replicated DNA, DNA strand breaks, or other abnormalities, and translate these DNA-derived stimuli into biochemical signals that modulate the functions of specific downstream target proteins. Expand
Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine.
Caffeine inhibits the catalytic activity of both ATM and the related kinase, ATM and Rad3-related (ATR), at drug concentrations similar to those that induce radiosensitization, suggesting that both proteins are relevant targets for the development of novel anticancer agents. Expand
A role for ATR in the DNA damage-induced phosphorylation of p53.
Evidence that the ATM-Rad3-related protein ATR regulates phosphorylation of Ser-15 in DNA-damaged cells is provided and it is suggested that p53 is a target for phosphorylated by ATR by blocking UV-induced Ser- 15 phosphorylations in a time-independent manner. Expand
Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism.
4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylated of the carboxy-terminal serum-sensitive sites, including those that interact with eIF4E. Expand
Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin
These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress. Expand
Genetic Evidence for Differential Coupling of Syk Family Kinases to the T-Cell Receptor: Reconstitution Studies in a ZAP-70-Deficient Jurkat T-Cell Line
In isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from the Jurkat T-cell line, transfection experiments with Zap-70–Syk chimeric proteins indicated that both the amino- terminal regulatory regions and the carboxy-terminal catalytic domains of Syk and Z AP-70 contribute to the distinctive functional properties of these PTKs. Expand
Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3‐kinase inhibitors, wortmannin and LY294002.
It is demonstrated that mTOR is a component of a cytokine‐triggered protein kinase cascade leading to the phosphorylation of the eukaryotic initiation factor‐4E (eIF‐4 E) binding protein, PHAS‐1, in activated T lymphocytes. Expand
A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.
It is demonstrated that interleukin-3 stimulation induces a wortmannin-sensitive increase in mTOR kinase activity in a myeloid progenitor cell line, and that the activation status of the PI3K-AKT pathway in cancer cells may be an important determinant of cellular sensitivity to the cytostatic effect of rapamycin. Expand
Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase.
Kinetic analysis demonstrates that wortmannin is a noncompetitive, irreversible inhibitor of phosphatidylinositol-3-kinase, with inactivation being both time- and concentration-dependent. Expand