Regulation of PKR activation and apoptosis during oxidative stress by TRBP phosphorylation
| Autor: | Benedicth Ukhueduan, Rekha C. Patel, Evelyn Chukwurah |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
viruses Response element Apoptosis environment and public health Biochemistry Article 03 medical and health sciences Transactivation Mice eIF-2 Kinase 0302 clinical medicine Cellular stress response Animals Humans Phosphorylation Protein kinase A RNA Double-Stranded Activator (genetics) Chemistry virus diseases RNA-Binding Proteins Cell Biology biochemical phenomena metabolism and nutrition Protein kinase R Cell biology enzymes and coenzymes (carbohydrates) Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis Signal transduction HeLa Cells Signal Transduction |
| Zdroj: | Int J Biochem Cell Biol |
| ISSN: | 1878-5875 |
| Popis: | Transactivation response element RNA-binding protein (TRBP or TARBP2) originally identified as a pro-viral cellular protein in human immunodeficiency virus (HIV) replication is also a regulator of microRNA biogenesis and cellular stress response. TRBP inhibits the catalytic activity of interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral infections and cell stress thereby regulating stress-induced signaling pathways. During cellular stress, PKR is catalytically activated transiently by its protein activator PACT and TRBP inhibits PKR to bring about a timely cellular recovery. We have previously established that TRBP phosphorylated after oxidative stress binds to and inhibits PKR more efficiently promoting cell survival. In this study, we investigated if phosphorylation of TRBP enhances its interaction with PACT to bring about additional PKR inhibition. Our data establishes that phosphorylation of TRBP has no effect on PACT-TRBP interaction and TRBP's inhibitory actions on PKR are mediated exclusively by its enhanced interaction with PKR. Cells lacking TRBP are more sensitive to apoptosis in response to oxidative stress and show persistent PKR activation. These results establish that PKR inhibition by stress-induced TRBP phosphorylation occurs by its direct binding to PKR and is important for preventing apoptosis due to sustained PKR activation. |
| Databáze: | OpenAIRE |
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