Journal ArticleDOI
The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Yosef Shiloh,Yael Ziv +1 more
TLDR
Evidence suggests that ATM-mediated phosphorylation has a role in the response to other types of genotoxic stress and it has become apparent that ATM is active in other cell signalling pathways involved in maintaining cellular homeostasis.Abstract:
The protein kinase ataxia-telangiectasia mutated (ATM) is best known for its role as an apical activator of the DNA damage response in the face of DNA double-strand breaks (DSBs). Following induction of DSBs, ATM mobilizes one of the most extensive signalling networks that responds to specific stimuli and modifies directly or indirectly a broad range of targets. Although most ATM research has focused on this function, evidence suggests that ATM-mediated phosphorylation has a role in the response to other types of genotoxic stress. Moreover, it has become apparent that ATM is active in other cell signalling pathways involved in maintaining cellular homeostasis.read more
Citations
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Journal ArticleDOI
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.
TL;DR: A historical perspective of their discovery is provided and their established functions in sensing and responding to genotoxic stress are discussed, as well as emerging non-canonical roles and how knowledge of ATM, ATR, and DNA-PK is being translated to benefit human health.
Journal ArticleDOI
Senescent cells: an emerging target for diseases of ageing.
Bennett G. Childs,Martina Gluscevic,Darren J. Baker,Remi-Martin Laberge,Dan Marquess,Jamie Dananberg,Jan M. van Deursen +6 more
TL;DR: Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.
Journal ArticleDOI
Metabolic targets for cancer therapy
Lorenzo Galluzzi,Lorenzo Galluzzi,Oliver Kepp,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Guido Kroemer +5 more
TL;DR: The intimate relationship between metabolism and malignancy is discussed, focusing on strategies through which this central aspect of tumour biology might be turned into cancer's Achilles heel.
Journal ArticleDOI
ATM and ATR as therapeutic targets in cancer.
Anika M. Weber,Anderson J. Ryan +1 more
TL;DR: Preclinical data have provided a strong rationale for clinical testing of these compounds both in combination with radio- or chemotherapy, and in synthetic lethal approaches to treat tumours with deficiencies in certain DDR components, suggesting that a synthetic lethal approach with ATM or ATR inhibitors could have widespread utility, providing that appropriate biomarkers are developed.
Journal ArticleDOI
p53 in the DNA-Damage-Repair Process
TL;DR: It appears as if p53 is multitasking in providing protection from cancer development by maintaining genome stability by overseeing the activity of various DNA-repair systems.
References
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mTOR Signaling in Growth Control and Disease
TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
Journal ArticleDOI
mTOR signaling in growth control and disease.
TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
Journal ArticleDOI
The DNA Damage Response: Making It Safe to Play with Knives
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.
Journal ArticleDOI
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
TL;DR: It is shown that ATM is held inactive in unirradiated cells as a dimer or higher-order multimer, with the kinase domain bound to a region surrounding serine 1981 that is contained within the previously described ‘FAT’ domain.
Journal ArticleDOI
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
TL;DR: This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival, ROS homeostasis and antioxidant gene regulation, mitochondrial oxidative stress, apoptosis, and aging.
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