Bibliographic Details
| Title: |
Inhibition of Ribosome Biogenesis In Vivo Causes p53-Dependent Death and p53-Independent DysfunctionSummary |
| Authors: |
Charles J. Cho, Thanh Nguyen, Amala K. Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L. Meier, Jason C. Mills |
| Source: |
Cellular and Molecular Gastroenterology and Hepatology, Vol 19, Iss 7, Pp 101496- (2025) |
| Publisher Information: |
Elsevier, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Diseases of the digestive system. Gastroenterology |
| Subject Terms: |
Ribosome, N-Acetyltransferase 10, Nucleolus, p53, Paligenosis, Diseases of the digestive system. Gastroenterology, RC799-869 |
| More Details: |
Background & Aims: Although it is well-known that ribosomes are critical for cell function, and their synthesis (known as ribosome biogenesis [RiBi]) is energy-intensive, surprisingly little is known about RiBi in vivo in adult tissue. Methods: Using a mouse model with conditional deletion of Nat10, an essential gene for RiBi and subsequent translation of mRNA, we investigated the effects of RiBi blockade in vivo, with a focus on pancreatic acinar cells during homeostasis and tumorigenesis. Results: We observed an unexpected latency of several weeks between Nat10 deletion and onset of structural and functional abnormalities and p53-dependent acinar cell death. Although deletion of Trp53 rescued acinar cells from apoptotic cell death, Nat10Δ/Δ; Trp53Δ/Δ acinar cells remained morphologically and functionally abnormal. Deletion of Nat10 in acinar cells blocked Kras-oncogene-driven pancreatic ductal adenocarcinoma, regardless of Trp53 mutation status. Conclusions: Together, our results provide initial insights into how differentiated cells respond to defects in RiBi and translation in vivo in various physiological contexts. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2352-345X |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2352345X25000372; https://doaj.org/toc/2352-345X |
| DOI: |
10.1016/j.jcmgh.2025.101496 |
| Access URL: |
https://doaj.org/article/3a48b76fcc9d4f1d8a94021484fdd1dd |
| Accession Number: |
edsdoj.3a48b76fcc9d4f1d8a94021484fdd1dd |
| Database: |
Directory of Open Access Journals |
