ArticleNucleic acids research2019
ITCH nuclear translocation and H1.2 polyubiquitination negatively regulate the DNA damage response.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- ITCH-Mediated Ubiquitination and Degradation of THBS1: A Key Mechanism for Enhancing Mitochondrial Biogenesis and Alleviating Mouse Skeletal Muscle Atrophy.Acta physiologica (Oxford, England) · 2026Article
- ATP2B4 driven chromatin compaction exacerbates pancreatic cancer radiotherapy resistance.Cell death discovery · 2026Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- TREM1 facilitates nonresponse to anti-TNF-α monoclonal antibodies in colitis via boosting ITCH/TAK1/caspase-8 axis-mediated macrophage pyroptosis.Journal of translational medicine · 2025Article
- Review
- USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.Acta pharmaceutica Sinica. B · 2025Article
- Role and therapeutic potential of the NEDD4 family in breast cancer.Frontiers in pharmacology · 2025Review
- Dot1l cooperates with Npm1 to repress endogenous retrovirus MERVL in embryonic stem cells.Nucleic acids research · 2023Article
- Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress.eLife · 2023Article
- Combining molecular dynamics simulations and scoring method to computationally model ubiquitylated linker histones in chromatosomes.PLoS computational biology · 2023Article
- Acetylation, Phosphorylation, Ubiquitination (Oh My!): Following Post-Translational Modifications on the Ubiquitin Road.Biomolecules · 2022Review
- The regulatory roles of the E3 ubiquitin ligase NEDD4 family in DNA damage response.Frontiers in physiology · 2022Review
- The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis.Translational cancer research · 2021Article
- Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.Frontiers in oncology · 2021Review
- Molecular and Cellular Functions of the Linker Histone H1.2.Frontiers in cell and developmental biology · 2021Review
- ITCH as a potential therapeutic target in human cancers.Seminars in cancer biology · 2020Review
- The role of E3 ubiquitin ligase HECTD3 in cancer and beyond.Cellular and molecular life sciences : CMLS · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, which plays important roles in DDR. Consistent with these findings, impaired ITCH nuclear translocation and H1.2 polyubiquitination sensitized cells to replication stress and limited cell growth and migration. AKT activation of ITCH-H1.2 axis may confer TNBC cells with a DDR repression to counteract the replication stress and increase cancer cell survivorship and growth potential.
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Registered trials
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.