AI Article Synopsis
- The USP1 enzyme has a crucial region for its function which was studied after a mutation was found in endometrial cancer.
- The mutation at Asp-199 (D199A) makes the enzyme unable to perform its role, unable to cleave itself or bind to ubiquitin properly, leading to issues with DNA repair processes.
- Results show that Asp-199 is vital for USP1's activity, pointing to potential consequences of reduced USP1 function in cancer development.
Article Abstract
The deubiquitinating enzyme USP1 contains highly conserved motifs forming its catalytic center. Recently, the COSMIC mutation database identified a mutation in USP1 at Asp-199 in endometrial cancer. Here, we investigated the role of Asp-199 for USP1 function. The mutation of aspartic acid to alanine (D199A) resulted in failure of USP1 to undergo autocleavage and form a complex with ubiquitin, indicating D199A Usp1 is catalytically inactive. The D199A mutation did not affect the interaction with Uaf1. Moreover, D199A Usp1 had defects in deubiquitination of FANCD2 and PCNA and displayed reduced FANCD2 foci formation and DNA repair efficiency. Furthermore, mutation of Asp-199 to glutamic acid resulted in phenotypes similar to the D199A mutation. Collectively, our findings demonstrate the importance of Asp-199 for USP1 activity and suggest the implications of USP1 downregulation in cancer.
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| http://dx.doi.org/10.1002/1873-3468.14152 | DOI Listing |
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