FicD Sensitizes Cellular Response to Glucose Fluctuations in Mouse Embryonic Fibroblasts.
Burak GulenLisa N KinchKelly A ServageAubrie BlevinsNathan M StewartHillery F GrayAmanda K CaseyKim OrthPublished in: bioRxiv : the preprint server for biology (2024)
The chaperone BiP plays a key quality control role in the endoplasmic reticulum, the cellular location for the production, folding, and transport of secreted proteins. The enzyme FicD regulates BiP's activity through AMPylation and deAMPylation. Our study unveils the importance of FicD in regulating BiP and the unfolded protein response (UPR) during stress. We identify distinct BiP AMPylation signatures for different stressors, highlighting FicD's nuanced control. Deletion of FicD causes widespread gene expression changes, disrupts UPR signaling, alters stress recovery, and perturbs protein secretion in cells. These observations underscore the pivotal contribution of FicD for preserving secretory protein homeostasis. Our findings deepen the understanding of FicD's role in maintaining cellular resilience and open avenues for therapeutic strategies targeting UPR-associated diseases.
Keyphrases
- endoplasmic reticulum
- gene expression
- quality control
- induced apoptosis
- protein protein
- dna methylation
- endoplasmic reticulum stress
- binding protein
- minimally invasive
- type diabetes
- heat stress
- genome wide
- signaling pathway
- oxidative stress
- small molecule
- cell death
- stress induced
- blood glucose
- molecular dynamics simulations
- social support
- cancer therapy