ArticleEMBO reports2021
Insert L1 is a central hub for allosteric regulation of USP1 activity.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Fine-Tuning Protein Fate: Mechanisms of E1, E2, and E3 Enzymes and Deubiquitinases in Cell Signaling.International journal of molecular sciences · 2026Review
- Disrupting the USP1-UAF1 deubiquitinase complex: a master regulator of replication stress and frontier target in cancer therapy.Medical oncology (Northwood, London, England) · 2026Review
- Molecular Mechanisms of the Ubiquitin-Specific Proteases (USPs) Family in Biliary Tract Cancer and Targeted Intervention Strategies.Biomedicines · 2025Review
- DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs.Nucleic acids research · 2025Article
- Survivin Is a Central Mediator of Cell Proliferation in HPV-Negative Head and Neck Squamous Cell Carcinoma.Cancers · 2025Article
- USP1 inhibition: A journey from target discovery to clinical translation.Pharmacology & therapeutics · 2025Review
- ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis.Cancer gene therapy · 2024Review
- Variety in the USP deubiquitinase catalytic mechanism.Life science alliance · 2024Article
- CAF-1 deposits newly synthesized histones during DNA replication using distinct mechanisms on the leading and lagging strands.Nucleic acids research · 2023Article
- Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site.Science advances · 2022Article
- [Regulatory effects of bio-intensity electric field on transformation of human skin fibroblasts].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Article
- Insert L1 is a central hub for allosteric regulation of USP1 activity.EMBO reports · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During DNA replication, the deubiquitinating enzyme USP1 limits the recruitment of translesion polymerases by removing ubiquitin marks from PCNA to allow specific regulation of the translesion synthesis (TLS) pathway. USP1 activity depends on an allosteric activator, UAF1, and this is tightly controlled. In comparison to paralogs USP12 and USP46, USP1 contains three defined inserts and lacks the second WDR20-mediated activation step. Here we show how inserts L1 and L3 together limit intrinsic USP1 activity and how this is relieved by UAF1. Intriguingly, insert L1 also conveys substrate-dependent increase in USP1 activity through DNA and PCNA interactions, in a process that is independent of UAF1-mediated activation. This study establishes insert L1 as an important regulatory hub within USP1 necessary for both substrate-mediated activity enhancement and allosteric activation upon UAF1 binding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.