The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway
Open accessAbstract
Stabilization of mutant p53 (mutp53) in tumours greatly contributes to malignant progression. However, little is known about the underlying mechanisms and therapeutic approaches to destabilize mutp53. Here, through high-throughput screening we identify statins, cholesterol-lowering drugs, as degradation inducers for conformational or misfolded p53 mutants with minimal effects on wild-type p53 (wtp53) and DNA contact mutants. Statins preferentially suppress mutp53-expressing cancer cell growth. Specific reduction of mevalonate-5-phosphate by statins or mevalonate kinase knockdown induces CHIP ubiquitin ligase-mediated nuclear export, ubiquitylation, and degradation of mutp53 by impairing interaction of mutp53 with DNAJA1, a Hsp40 family member. Knockdown of DNAJA1 also induces CHIP-mediated mutp53 degradation, while its overexpression antagonizes statin-induced mutp53 degradation. Our study reveals that DNAJA1 controls the fate of misfolded mutp53, provides insights into potential strategies to deplete mutp53 through the mevalonate pathway–DNAJA1 axis, and highlights the significance of p53 status in impacting statins’ efficacy on cancer therapy.
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
“Surprisingly, statins can decrease the levels of mevalonate-5-phosphate and prevent mutated p53 from binding to HSPs, thus promoting the degradation of structural p53 mutants by MDM2 or CHIP E3.382,383”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [382]
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
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804
Ubiquitination and Degradation of Mutant p53
Lukashchuk, N., & Vousden, K. H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00050-07 · Cited by 223
Hiraki, M., Hwang, S.-Y., Cao, S., Ramadhar, T. R., Byun, S., Yoon, K. W., Lee, J. H., Chu, K., Gurkar, A. U., Kolev, V., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.07.016 · Cited by 81
Cited by
Mutant p53 in cancer: from molecular mechanism to therapeutic modulation
Chen, X., Zhang, T., Su, W., Dou, Z., Zhao, D., Jin, X., Lei, H., Wang, J., Xie, X., Cheng, B., et al. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-05408-1 · Cited by 494
van der Kant, R., Langness, V. F., Herrera, C. M., Williams, D. A., Fong, L. K., Leestemaker, Y., Steenvoorden, E., Rynearson, K. D., Brouwers, J. F., Helms, J. B., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2018.12.013 · Cited by 350
Statins as Anticancer Agents in the Era of Precision Medicine
Longo, J., van Leeuwen, J. E., Elbaz, M., Branchard, E., & Penn, L. Z. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1967 · Cited by 196
p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression
Ghosh, M., Saha, S., Li, J., Montrose, D. C., & Martinez, L. A. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.023 · Cited by 166
Drugs Targeting p53 Mutations with FDA Approval and in Clinical Trials
Nishikawa, S., & Iwakuma, T. (2023) · Cancers · doi:10.3390/cancers15020429 · Cited by 115
Self-citation
Metadata
- Authors
- Parrales, A., Ranjan, A., Iyer, S. V., Padhye, S., Weir, S. J., Roy, A., & Iwakuma, T.
- Venue
- Nature Cell Biology
- Published
- 2016-10-24
- Volume
- 18
- Issue
- 11
- Pages
- 1233-1243
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2532024005
- Cited by
- 239
- References
- 3
- FWCI
- 11.28
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. https://app.cochat.ai/papers/10.1038/ncb3427
- The paper
- Parrales, A., Ranjan, A., Iyer, S. V., Padhye, S., Weir, S. J., Roy, A., & Iwakuma, T. (2016). DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. Nature Cell Biology. https://doi.org/10.1038/ncb3427
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
