Usage Information
Citation Information: J Clin Invest. 2010;120(7):2549-2562. https://doi.org/10.1172/JCI41933.
Abstract
Despite significant advancements in our understanding of cancer development, the molecular mechanisms that underlie the formation of liver cancer remain largely unknown. C/EBPα is a transcription factor that regulates liver quiescence. Phosphorylation of C/EBPα at serine 193 (S193-ph) is upregulated in older mice and is thought to contribute to age-associated liver dysfunction. Because development of liver tumors is associated with increasing age, we investigated the role of S193-ph in the development of liver cancer using knockin mice expressing a phospho-mimetic aspartic acid residue in place of serine at position 193 (S193D) of C/EBPα. The S193D isoform of C/EBPα was able to completely inhibit liver proliferation in vivo after partial hepatectomy. However, treatment of these mice with diethylnitrosamine/phenobarbital (DEN/PB), which induces formation of liver cancer, actually resulted in earlier development of liver tumors. DEN/PB treatment was associated with specific degradation of both the S193-ph and S193D isoforms of C/EBPα through activation of the ubiquitin-proteasome system (UPS). The mechanism of UPS-mediated elimination of C/EBPα during carcinogenesis involved elevated levels of gankyrin, a protein that was found to interact with the S193-ph isoform of C/EBPα and target it for UPS-mediated degradation. This study identifies a molecular mechanism that supports the development of liver cancer in older mice and potential therapeutic targets for the prevention of liver cancer.
Authors
Guo-Li Wang, Xiurong Shi, Simon Haefliger, Jingling Jin, Angela Major, Polina Iakova, Milton Finegold, Nikolai A. Timchenko
Usage data is cumulative from June 2024 through June 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 260 | 41 |
| 53 | 19 | |
| Figure | 286 | 5 |
| Table | 35 | 0 |
| Supplemental data | 37 | 3 |
| Citation downloads | 57 | 0 |
| Totals | 728 | 68 |
| Total Views | 796 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)