Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: A truncating mutation in the autophagy gene UVRAG drives inflammation and tumorigenesis in mice.

Authors: Quach, Christine; Song, Ying; Guo, Hongrui; Li, Shun; Maazi, Hadi; Fung, Marshall; Sands, Nathaniel; O'Connell, Douglas; Restrepo-Vassalli, Sara; Chai, Billy; Nemecio, Dali; Punj, Vasu; Akbari, Omid; Idos, Gregory E; Mumenthaler, Shannon M; Wu, Nancy; Martin, Sue Ellen; Hagiya, Ashley; Hicks, James; Cui, Hengmin; Liang, Chengyu

Published In Nat Commun, (2019 12 12)

Abstract: Aberrant autophagy is a major risk factor for inflammatory diseases and cancer. However, the genetic basis and underlying mechanisms are less established. UVRAG is a tumor suppressor candidate involved in autophagy, which is truncated in cancers by a frameshift (FS) mutation and expressed as a shortened UVRAGFS. To investigate the role of UVRAGFS in vivo, we generated mutant mice that inducibly express UVRAGFS (iUVRAGFS). These mice are normal in basal autophagy but deficient in starvation- and LPS-induced autophagy by disruption of the UVRAG-autophagy complex. iUVRAGFS mice display increased inflammatory response in sepsis, intestinal colitis, and colitis-associated cancer development through NLRP3-inflammasome hyperactivation. Moreover, iUVRAGFS mice show enhanced spontaneous tumorigenesis related to age-related autophagy suppression, resultant β-catenin stabilization, and centrosome amplification. Thus, UVRAG is a crucial autophagy regulator in vivo, and autophagy promotion may help prevent/treat inflammatory disease and cancer in susceptible individuals.

PubMed ID: 31831743 Exiting the NIEHS site

MeSH Terms: Animals; Autophagy/genetics*; Carcinogenesis/genetics*; Carcinogenesis/pathology; Cell Proliferation; Centrosome; Colitis; Colonic Neoplasms/pathology; Colorectal Neoplasms/genetics; Female; Frameshift Mutation; Inflammasomes; Inflammation/genetics*; Lipopolysaccharides/adverse effects; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation*; NLR Family, Pyrin Domain-Containing 3 Protein; Sepsis; Starvation; Toll-Like Receptor 4/metabolism; Tumor Suppressor Proteins/genetics*

Back
to Top