The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression
Open accessPublished version of a preprint
Abstract
Tumor suppression by TP53 involves cell-autonomous and non-cell-autonomous mechanisms. TP53 can suppress tumor growth by modulating immune system functions; however, the mechanistic basis for this activity is not well understood. We report that p53 promotes the degradation of the DNA exonuclease TREX1, resulting in cytosolic dsDNA accumulation. We demonstrate that p53 requires the ubiquitin ligase TRIM24 to induce TREX1 degradation. The cytosolic DNA accumulation resulting from TREX1 degradation activates the cytosolic DNA-sensing cGAS/STING pathway, resulting in induction of type I interferons. TREX1 overexpression sufficed to block p53 activation of the cGAS/STING pathway. p53-mediated induction of type I interferon (IFNB1) is suppressed by cGAS/STING knockout, and p53's tumor suppressor activities are compromised by the loss of signaling through the cGAS/STING pathway. Thus, our study reveals that p53 utilizes the cGAS/STING innate immune system pathway for both cell-intrinsic and cell-extrinsic tumor suppressor activities.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Links between IL-1 signalling and p53 have been reported in the context of tumour cells 68,69 , and the cGAS-STING axis is increasingly linked to DNA damage 70 , although the exact triggers of this pathway in the context of AAV-mediated CNS transduction remain to be defined.”
From AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain (2025) · cites this paper as [70]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234
Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
Sun, L., Wu, J., Du, F., Chen, X., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1232458 · Cited by 4,996
Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329
IKKε and TBK1 are essential components of the IRF3 signaling pathway
Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003) · Nature Immunology · doi:10.1038/ni921 · Cited by 2,680
Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
Wu, J., Sun, L., Chen, X., Du, F., Shi, H., Chen, C., & Chen, Z. J. (2012) · Science · doi:10.1126/science.1229963 · Cited by 2,628
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
T antigen is bound to a host protein in SY40-transformed cells
Lane, D. P., & Crawford, L. V. (1979) · Nature · doi:10.1038/278261a0 · Cited by 2,456
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401
Cited by
Sorted by citations
Understanding the complexity of p53 in a new era of tumor suppression
Liu, Y., Su, Z., Tavana, O., & Gu, W. J. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.04.009 · Cited by 538
Mitochondria-associated programmed cell death as a therapeutic target for age-related disease
Nguyễn, T. T., Wei, S., Nguyen, T. H., Jo, Y., Zhang, Y., Park, W., Gariani, K., Oh, C., Kim, H. H., Ha, K., et al. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01046-5 · Cited by 351
Translating p53-based therapies for cancer into the clinic
Peuget, S., Zhou, X., & Selivanova, G. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-023-00658-3 · Cited by 208
The balance of STING signaling orchestrates immunity in cancer
Lanng, K. R. B., Lauridsen, E. L., & Jakobsen, M. R. (2024) · Nature Immunology · doi:10.1038/s41590-024-01872-3 · Cited by 179
“The degradation of TREX1 mediated by p53, thus increases cytosolic DNA accumulation and STING activation 45 .”
TREX1 Inactivation Unleashes Cancer Cell STING–Interferon Signaling and Promotes Antitumor Immunity
Tani, T., Mathsyaraja, H., Campisi, M., Li, Z., Haratani, K., Fahey, C. G., Ota, K., Mahadevan, N. R., Shi, Y., Saito, S., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0700 · Cited by 116
Metadata
- Authors
- Ghosh, M., Saha, S., Li, J., Montrose, D. C., & Martinez, L. A.
- Affiliations
- Stony Brook University (US)
- Stony Brook Medicine (US)
- Corresponding author
- Martinez, Luis A.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 83
- Issue
- 2
- Pages
- 266-280.e6
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC9993620
- OpenAlex
- W4315705275
- Cited by
- 166
- References
- 60
- Citations by year
- 2026: 48 · 2025: 54 · 2024: 37 · 2023: 27
- FWCI
- 18.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 383 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Stony Brook University
- National Institutes of Health
- National Cancer Institute (K22CA226033, R01CA166974)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- TP53, p53, cGAS-STING pathway, cytosolic DNA sensing, TRIM24, type I interferon, IFNB1, tumor suppression, innate immunity, double-stranded DNA, ubiquitin ligase
- MeSH terms
- STING Protein, DNA, Immunity, Innate, Interferon Type I, Membrane Proteins, Nucleotidyltransferases, Signal Transduction, Tumor Suppressor Protein p53
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
