| First Author | Piatkov KI | Year | 2012 |
| Journal | Mol Cell | Volume | 48 |
| Issue | 6 | Pages | 926-33 |
| PubMed ID | 23159736 | Mgi Jnum | J:194097 |
| Mgi Id | MGI:5470341 | Doi | 10.1016/j.molcel.2012.10.012 |
| Citation | Piatkov KI, et al. (2012) The auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway. Mol Cell 48(6):926-33 |
| abstractText | Deamidation of N-terminal Gln by the Ntaq1 Nt(Q)-amidase is a part of the Arg/N-end rule pathway, a ubiquitin-dependent proteolytic system. Here we identify Gln-Usp1(Ct), the C-terminal fragment of the autocleaved Usp1 deubiquitylase, as the first physiological Arg/N-end rule substrate that is targeted for degradation through deamidation of N-terminal Gln. Usp1 regulates genomic stability, in part through the deubiquitylation of monoubiquitylated PCNA, a DNA polymerase processivity factor. The autocleaved Usp1 remains a deubiquitylase because its fragments remain associated with Uaf1, an enhancer of Usp1 activity, until the Gln-Usp1(Ct) fragment is selectively destroyed by the Arg/N-end rule pathway. We also show that metabolic stabilization of Gln-Usp1(Ct) results in a decreased monoubiquitylation of PCNA and in a hypersensitivity of cells to ultraviolet irradiation. Thus, in addition to its other functions in DNA repair and chromosome segregation, the Arg/N-end rule pathway regulates genomic stability through the degradation-mediated control of the autocleaved Usp1 deubiquitylase. |
