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Radyk, M. D., Spatz, L. B., & Peña, B. L. (2021). Atf3 induces rab7 to govern autodegradation in paligenosis, a conserved cell plasticity program. EMBO reports, 22(9), e51806. 
Added by: Dr. Enrique Feoli (25/05/2023, 13:43)   Last edited by: Dr. Enrique Feoli (25/05/2023, 13:47)
Resource type: Journal Article
DOI: https://doi.org/10.15252/embr.202051806
BibTeX citation key: Radyk2021
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 Categories: BioAcyl Corp
Subcategories: Cell plasticity
Creators: Peña, Radyk, Spatz
Collection: EMBO reports		 Views: 1/132
Abstract
Abstract Differentiated cells across multiple species and organs can re-enter the cell cycle to aid in injury-induced tissue regeneration by a cellular program called paligenosis. Here, we show that activating transcription factor 3 (ATF3) is induced early during paligenosis in multiple cellular contexts, transcriptionally activating the lysosomal trafficking gene Rab7b. ATF3 and RAB7B are upregulated in gastric and pancreatic digestive-enzyme-secreting cells at the onset of paligenosis Stage 1, when cells massively induce autophagic and lysosomal machinery to dismantle differentiated cell morphological features. Their expression later ebbs before cells enter mitosis during Stage 3. Atf3–/– mice fail to induce RAB7-positive autophagic and lysosomal vesicles, eventually causing increased death of cells en route to Stage 3. Finally, we observe that ATF3 is expressed in human gastric metaplasia and during paligenotic injury across multiple other organs and species. Thus, our findings indicate ATF3 is an evolutionarily conserved gene orchestrating the early paligenotic autodegradative events that must occur before cells are poised to proliferate and contribute to tissue repair.
  
Notes

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Pancreatic and gastric exocrine cells regenerate after injury through a process called paligenosis. Injury-induced ATF3 promotes cell autodegradation via transcriptional activation of Rab7b, a regulator of late endosomal and lysosomal trafficking. Atf3 upregulation in injury across diverse organs and species suggests a conserved role in governing the cell plasticity program of paligenosis.

 

  • ATF3 transcriptionally activates Rab7b during paligenotic autodegradation of exocrine cells of the stomach and pancreas.
  • Atf3 is required for lysosome and autophagy induction in paligenosis.
  • Atf3 loss leads to increased cell death during paligenosis and decreased tissue repair following injury.

Added by: Dr. Enrique Feoli  Last edited by: Dr. Enrique Feoli
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