| Autor: |
Louis R. Parham, Patrick A. Williams, Priya Chatterji, Kofi K. Acheampong, Charles H. Danan, Kay Katada, Xianghui Ma, Lauren A. Simon, Kaitlyn E. Naughton, Rei Mizuno, Tatiana Karakasheva, Emily A. McMillan, Kelly A. Whelan, Donita C. Brady, Sydney M. Shaffer, Kathryn E. Hamilton |
| Rok vydání: |
2022 |
| Popis: |
Homeostatic tissue maintenance requires coordinated regulation of metabolic processes including macroautophagy/autophagy. Autophagy dysregulation underlies numerous human diseases. Our prior work revealed that the RNA binding protein IGF2BP1/IMP1 binds transcripts encoding autophagy-related proteins. Furthermore, Imp1 deletion in gastrointestinal epithelial cells in mice was associated with enhanced autophagy flux and improved recovery from tissue injury. In the current study, we evaluated molecular mechanisms underlying IMP1 modulation of autophagy. We provide a mechanism of direct IMP1 regulation of MAP1LC3B that is dependent upon IMP1 phosphorylation or cell stress, suggesting dynamic modulation of Imp1-mediated autophagy repression that facilitates tissue regeneration. More broadly, our study supports a new mechanism by which tissue regeneration is modulated post-transcriptionally via cell state rather than changes in stem or other cell lineages. This new mechanism may be particularly important in gastrointestinal epithelial cells, where autophagy is essential for tissue recovery following injury, or in diseases such as inflammatory bowel disease where defective autophagy is implicated. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
