AI Article Synopsis
- The study identified USP49 as a new deubiquitinase (DUB) that enhances the stability and activity of the p53 tumor suppressor in response to DNA damage.
- USP49 interacts with the N terminus of p53, reducing its ubiquitination and increasing p53's effectiveness in regulating genes involved in the DNA damage response.
- USP49 is upregulated during cell stress and is linked to increased sensitivity to etoposide, highlighting its potential role as a tumor suppressor in a feedback loop with p53, especially in a mouse model prone to colon tumors.
Article Abstract
The p53 tumor suppressor is a critical factor in the DNA damage response (DDR), and regulation of p53 stability has a key role in this process. In our study, we identified USP49 as a novel deubiquitinase (DUB) for p53 from a library consisting of 80 DUBs and found that USP49 has a positive effect on p53 transcriptional activity and protein stability. Investigation of the mechanism revealed that USP49 interacts with the N terminus of p53 and suppresses several types of p53 ubiquitination. Furthermore, USP49 rendered HCT116 cells more sensitive to etoposide (Eto)-induced DNA damage and was upregulated in response to several types of cell stress, including DNA damage. Remarkably, USP49 expression was regulated by p53 and USP49 in knockout mice, which are more susceptible to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumors. These findings suggest that USP49 has an important role in DDR and may act as a potential tumor suppressor by forming a positive feedback loop with p53.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945681 | PMC |
| http://dx.doi.org/10.1038/s41419-018-0475-3 | DOI Listing |
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