Abstract
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is known as a tumor suppressor gene that is frequently mutated in numerous human cancers and inherited syndromes. PTEN functions as a negative regulator of PI3K/Akt signaling pathway by dephosphorylating phosphatidylinositol (3, 4, 5)-trisphosphate (PIP3) to phosphatidylinositol (4, 5)-bisphosphate (PIP2), which leads to the inhibition of cell growth, proliferation, cell survival, and protein synthesis. PTEN contains a cysteine residue in the active site that can be oxidized by peroxides, forming an intramolecular disulfide bond between Cys124 and Cys71. Redox regulation of PTEN by reactive oxygen species (ROS) plays a crucial role in cellular signaling. Peroxiredoxins (Prxs) are a superfamily of peroxidase that catalyzes reduction of peroxides and maintains redox homeostasis. Mammalian Prxs have 6 isoforms (I-VI) and can scavenge cellular peroxides. It has been demonstrated that Prx I can preserve and promote the tumor-suppressive function of PTEN by preventing oxidation of PTEN under benign oxidative stress via direct interaction. Also, Prx II-deficient cells increased PTEN oxidation and insulin sensitivity. Furthermore, Prx III has been shown to protect PTEN from oxidation induced by 15s-HpETE and 12s-HpETE, these are potent inflammatory and pro-oxidant mediators. Understanding the tight connection between PTEN and Prxs is important for providing novel therapies. Herein, we summarized recent studies focusing on the relationship of Prxs and the redox regulation of PTEN.
Highlights
The phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is the critical intracellular signaling in controlling a variety of cellular processes [1]
The downstream signaling of the PI3K/Akt pathway was activated when the cell was stimulated with insulin, which triggers the activation of specific receptors, including the insulin receptor (IR) and insulin receptor substrate (IRS)
PTEN and protein tyrosine phosphatases (PTPs) all antagonize the insulin signaling as they directly interact with PI3K and IR [98], and both consist of a cysteine residue in the active site that is highly susceptible to H2 O2 -induced oxidation
Summary
The phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is the critical intracellular signaling in controlling a variety of cellular processes [1]. The signaling messenger function is exerted by triggering the reversible oxidation of the concentrations, ROS have positive effects by means of increasing cellular antioxidative regulatory proteins’. ROS are required for the regulation of irreversibe intracellular signaling, which affects various further reactions can happen that leads to oxidation and degradation of protein processes, including proliferation, cell survival, and other important events [14–. Possesses a PTEN cysteine in the phosphatase domain, it becomes a target of ROS, especially has an antagonizing function in the PI3K/Akt pathway by inhibiting the downhydrogen peroxide
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