ArticleCancer research2022
p16 Represses DNA Damage Repair via a Novel Ubiquitin-Dependent Signaling Cascade.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- TRIP12 promotes HIV-1 replication and latency reactivation by stabilizing Tat via USP7-mediated deubiquitination.Journal of virology · 2026Article
- COL11A2 Methylation as a Biomarker for Radiosensitivity and Microenvironment Remodelling in Oral Squamous Cell Carcinoma.International dental journal · 2026Article
- How Oncovirus Affects Drug Resistance in Cancer Cells.Recent patents on anti-cancer drug discovery · 2026Review
- Salivary gland cell senescence in Sjögren's syndrome: current research and novel therapeutic directions.Immunity & ageing : I & A · 2025Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer.Journal of the National Cancer Institute · 2025Article
- TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair.Nucleic acids research · 2025Article
- HPV-Mediated Radiosensitivity in Oropharyngeal Squamous Cell Carcinoma: Molecular Mechanisms and Cellular Pathways.Current oncology reports · 2025Review
- hTERT and SV40LgT Renal Cell Lines Adjust Their Transcriptional Responses After Copy Number Changes from the Parent Proximal Tubule Cells.International journal of molecular sciences · 2025Article
- Review
- Association of oropharyngeal cancer recurrence with tumor-intrinsic and immune-mediated sequelae of reduced genomic instability.bioRxiv : the preprint server for biology · 2024Article
- Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer.Cancer cell international · 2024Article
- Engineered targeting OIP5 sensitizes bladder cancer to chemotherapy resistance via TRIP12-PPP1CB-YBX1 axis.Oncogene · 2024Article
- The Causes and Consequences of DNA Damage and Chromosomal Instability Induced by Human Papillomavirus.Cancers · 2024Review
- USP7 Deregulation Impairs S Phase Specific DNA Repair after Irradiation in Breast Cancer Cells.Biomedicines · 2024Article
- [PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- FAK Drives Resistance to Therapy in HPV-Negative Head and Neck Cancer in a p53-Dependent Manner.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Moving from conventional to adaptive risk stratification for oropharyngeal cancer.Frontiers in oncology · 2024Review
- Histology Specific Molecular Biomarkers: Ushering in a New Era of Precision Radiation Oncology.Seminars in radiation oncology · 2023Review
- Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC).Cell death and differentiation · 2023Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Squamous cell carcinoma driven by human papillomavirus (HPV) is more sensitive to DNA-damaging therapies than its HPV-negative counterpart. Here, we show that p16, the clinically used surrogate for HPV positivity, renders cells more sensitive to radiotherapy via a ubiquitin-dependent signaling pathway, linking high levels of this protein to increased activity of the transcription factor SP1, increased HUWE1 transcription, and degradation of ubiquitin-specific protease 7 (USP7) and TRIP12. Activation of this pathway in HPV-positive disease led to decreased homologous recombination and improved response to radiotherapy, a phenomenon that can be recapitulated in HPV-negative disease using USP7 inhibitors in clinical development. This p16-driven axis induced sensitivity to PARP inhibition and potentially leads to "BRCAness" in head and neck squamous cell carcinoma (HNSCC) cells. Thus, these findings support a functional role for p16 in HPV-positive tumors in driving response to DNA damage, which can be exploited to improve outcomes in both patients with HPV-positive and HPV-negative HNSCC. SIGNIFICANCE: In HPV-positive tumors, a previously undiscovered pathway directly links p16 to DNA damage repair and sensitivity to radiotherapy via a clinically relevant and pharmacologically targetable ubiquitin-mediated degradation pathway.
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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.