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Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress.

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TLDR
PP5 appears to act as a physiological inhibitor of ASK1–JNK/p38 pathways by negative feedback and inhibited not only H2O2‐induced sustained activation of AsK1 but also ASK 1‐dependent apoptosis.
Abstract
Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase (MAPKKK) that activates the JNK and p38 MAP kinase cascades and is activated in response to oxidative stress such as hydrogen peroxide (H(2)O(2)). A yeast two-hybrid screening identified a serine/threonine protein phosphatase 5 (PP5) as a binding partner of ASK1. PP5 directly dephosphorylated an essential phospho-threonine residue within the kinase domain of ASK1 and thereby inactivated ASK1 activity in vitro and in vivo. The interaction between PP5 and ASK1 was induced by H(2)O(2) treatment and was followed by the decrease in ASK1 activity. PP5 inhibited not only H(2)O(2)-induced sustained activation of ASK1 but also ASK1-dependent apoptosis. Thus, PP5 appears to act as a physiological inhibitor of ASK1-JNK/p38 pathways by negative feedback.

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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.
Journal ArticleDOI

Redox Regulation of Cell Survival

TL;DR: The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed and the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases.
Journal ArticleDOI

Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis

TL;DR: This review highlights the basic mechanisms of ROS production and their sites of formation; detail mechanism of both mitochondria-dependent and mitochondrial-independent pathways of apoptosis as well as their regulation by ROS and describes the involvement of oxidative stress under various environmental toxin- and drug-induced organ pathophysiology and diabetes-mediated apoptosis.
Journal ArticleDOI

Mechanisms of cell death in oxidative stress.

TL;DR: Cell death mechanisms have been studied across a broad spectrum of models of oxidative stress, including H2O2, nitric oxide and derivatives, endotoxin-induced inflammation, photodynamic therapy, ultraviolet-A and ionizing radiations, and cigarette smoke.
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Hydrogen peroxide sensing, signaling and regulation of transcription factors

TL;DR: The multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.
References
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Journal ArticleDOI

Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis

TL;DR: The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells.
Journal ArticleDOI

Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation

Christopher J. Marshall
- 27 Jan 1995 - 
TL;DR: Experiments with PC12 cells suggest that the duration of ERK activation is critical for cell signaling decisions, and the extracellular signal-regulated kinase (ERK-regulated) MAPK pathway may be sufficient for these cellular responses.
Journal ArticleDOI

Signal transduction by the JNK group of MAP kinases.

TL;DR: This review will focus on the JNK group of MAP kinases, which are characterized by the sequence TEY and the two stress-activatedMAP kinases: p38 with the sequence TGY, and the c-Jun NH2-terminal kinases (JNK) with the sequences TPY.
Journal ArticleDOI

Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human

TL;DR: All known MAPK module kinases from yeast to humans are defined, what is known about their regulation, defined MAPK substrates, and the function of MAPK in cell physiology are defined.
Journal ArticleDOI

Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.

TL;DR: Evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine‐ and stress‐induced apoptosis.
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