ArticleThe Journal of clinical investigation2012
Chemosensitivity is controlled by p63 modification with ubiquitin-like protein ISG15.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The trial behind it
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- Understanding protein ISGylation, a multifaceted posttranslational modification.Cell chemical biology · 2026Review
- A Novel TP63 Missense Mutation in the Sumoylation Motif Causes Isolated Split-Hand/Foot Malformation 4: A Pedigree Report and Literature Review.Molecular genetics & genomic medicine · 2025Review
- ISG15 Enhances the Activity of γ-Glutamate Cysteine Ligase to Suppress Apoptosis in High Fat Diet-Promoted Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.Cell death discovery · 2025Article
- Nuclear translocation of ISG15 regulated by PPP2R2B inhibits cisplatin resistance of bladder cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.Experimental & molecular medicine · 2024Article
- A comparativeOncology research · 2024Article
- ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.International journal of biological sciences · 2024Article
- ISG15: A link between innate immune signaling, DNA replication, and genome stability.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- ISG15 suppresses ovulation and female fertility by ISGylating ADAMTS1.Cell & bioscience · 2023Article
- cGAS-STING signalling in cancer: striking a balance with chromosomal instability.Biochemical Society transactions · 2023Review
- Protein ISGylation: a posttranslational modification with implications for malignant neoplasms.Exploration of targeted anti-tumor therapy · 2023Review
- Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease.Frontiers in cell and developmental biology · 2023Review
- The diverse repertoire of ISG15: more intricate than initially thought.Experimental & molecular medicine · 2022Review
- ALTEN: A High-Fidelity Primary Tissue-Engineering Platform to Assess Cellular Responses Ex Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- WBSCR22 and TRMT112 synergistically suppress cell proliferation, invasion and tumorigenesis in pancreatic cancer via transcriptional regulation of ISG15.International journal of oncology · 2022Article
- Review
- Review
- Interferon-stimulated gene 15 accelerates replication fork progression inducing chromosomal breakage.The Journal of cell biology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identification of the cellular mechanisms that mediate cancer cell chemosensitivity is important for developing new cancer treatment strategies. Several chemotherapeutic drugs increase levels of the posttranslational modifier ISG15, which suggests that ISGylation could suppress oncogenesis. However, how ISGylation of specific target proteins controls tumorigenesis is unknown. Here, we identified proteins that are ISGylated in response to chemotherapy. Treatment of a human mammary epithelial cell line with doxorubicin resulted in ISGylation of the p53 family protein p63. An alternative splice variant of p63, ΔNp63α, suppressed the transactivity of other p53 family members, and its expression was abnormally elevated in various human epithelial tumors, suggestive of an oncogenic role for this variant. We showed that ISGylation played an essential role in the downregulation of ΔNp63α. Anticancer drugs, including doxorubicin, induced ΔNp63α ISGylation and caspase-2 activation, leading to cleavage of ISGylated ΔNp63α in the nucleus and subsequent release of its inhibitory domain to the cytoplasm. ISGylation ablated the ability of ΔNp63α to promote anchorage-independent cell growth and tumor formation in vivo as well to suppress the transactivities of proapoptotic p53 family members. These findings establish ISG15 as a tumor suppressor via its conjugation to ΔNp63α and provide a molecular rationale for therapeutic use of doxorubicin against ΔNp63α-mediated cancers.
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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.