biostudies-literaturePiatkov KINIDDK NIH HHSNIGMS NIH HHS926-33https://www.ebi.ac.uk/biostudies/studies/S-EPMC3889152biostudies-literatureUnknown48(6)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 monoubiquMolecular cellThe auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway.PMC3889152R56 DK039520R01 GM031530DK039520GM084244R01 GM084244GM031530R01 DK039520R37 DK039520Varshavsky AColnaghi LHuang TTPiatkov KIBekes MfalseThe auto-generated fragment of the Usp1 deubiquitylase is a physiological substrate of the N-end rule pathway.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 monoubiqu2012-01-01T00:00:00Z2012 Dec2025-04-04T21:13:32.295Z2019-03-27T01:19:53ZS-EPMC38891522315973610.1016/j.molcel.2012.10.012