Nuclear PTEN enhances the maturation of a microRNA regulon to limit MyD88-dependent susceptibility to sepsis
Year: 2018
Type: article
Abstract: deletion in an animal model of sepsis increased bacterial loads and cytokine production, which depended on enhanced myeloid differentiation primary response gene 88 (MyD88) abundance and resulted in mortality. PTEN-mediated induction of the microRNAs (miRNAs) miR125b and miR203b reduced the abundance of MyD88. Loss- and gain-of-function assays demonstrated that PTEN induced miRNA production by associating with and facilitating the nuclear localization of Drosha-Dgcr8, part of the miRNA-processing complex. Reconstitution of PTEN-deficient mouse embryonic fibroblasts with a mutant form of PTEN that does not localize to the nucleus resulted in retention of Drosha-Dgcr8 in the cytoplasm and impaired production of mature miRNAs. Thus, we identified a regulatory pathway involving nuclear PTEN-mediated miRNA generation that limits the production of MyD88 and thereby limits sepsis-associated mortality.
Source: Science Signaling
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Awards: G1751267823, Regulation of Toll-like receptor-induced NFkB activation by Gai-coupled receptors, Novel diagnostic and stratification tools for septic shock, Phosphatase and tensin homolog PTEN actions in polymicrobial sepsis, G4540434362, Stratification of pediatric septic shock, Regulation of Toll-like receptor-induced NFkB activation by Gai-coupled receptors, G6373640811, Association of receptors for lipid mediators with PRRs in macrophages and dendritic cells, Immunology and Infectious Diseases Training Program
OpenAlex ID: W2802681693