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Delineating The Mechanisms Of Misfolded Endoplasmic Reticulum (Er) Luminal Protein Retrotranslocation For Er-Associated Degradation, Christina Oikonomou
Delineating The Mechanisms Of Misfolded Endoplasmic Reticulum (Er) Luminal Protein Retrotranslocation For Er-Associated Degradation, Christina Oikonomou
Theses and Dissertations (ETD)
Secreted, plasma membrane, and resident proteins of the secretory pathway are synthesized in the endoplasmic reticulum (ER) where they undergo post-translational modifications, oxidative folding, and subunit assembly in tightly monitored processes. An ER quality control (ERQC) system oversees protein maturation and ensures that only those reaching their native state will continue trafficking into the secretory pathway to reach their final destinations. Proteins that fail quality control must be recognized and eliminated to maintain ER proteostasis. The ER-associated degradation (ERAD) was discovered nearly 30 years ago and entails the identification of improperly matured secretory pathway proteins and their retrotranslocation to the …
Transcriptional Regulation Of Nlrc4 Inflammasome By Irf8, Ein Lee
Transcriptional Regulation Of Nlrc4 Inflammasome By Irf8, Ein Lee
Theses and Dissertations (ETD)
The NLRC4 inflammasome is a crucial part of the innate immune response against bacterial infections. We found that NLRC4 inflammasome activation in bone marrow-derived macrophages (BMDMs) is greatly dependent on interferon regulatory factor 8 (IRF8). NLRC4-mediated caspase-1 activation and subsequent production of the inflammasome-dependent cytokines IL-1β and IL-18 and cell death were impaired in IRF8-deficient cells. IRF8 mediated the transcription of genes encoding NAIPs, the receptors for NLRC4 inflammasome, which recognize bacterial flagellin and type III secretion system (T3SS) proteins. IRF8 was critical for host survival following infection with Salmonella Typhimurium or Burkholderia thailandensis. Furthermore, mice deficient in IRF8 were …