The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73
Open accessAbstract
Protein degradation is an essential and highly regulated process. The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. Our findings provide the first evidence for in vivo degradation of p53 and p73 by the 20S proteasomes and its regulation by NQO1 and NADH level.
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
“Interestingly, the reduced form of NAD+, NADH, binds and stabilizes 26S proteasomes, and may also regulate the function of 20S proteasomes, the two main proteolytic complexes (Asher et al., 2005; Tsvetkov et al., 2014).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Asher et al., 2005
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
1 retracted
Long, D. J., Gaikwad, A. S., Multani, A. S., Pathak, S., Montgomery, C. A., Gonzalez, F. J., & Jaiswal, A. K. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-2455 · Cited by 112
RetractedHershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 2×
“Upon -irradiation, p53 undergoes post-translational modifications and escapes Mdm2-mediated degradation (Vogel- stein et al. 2000).”
BackgroundMdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 1×
“The tumor suppressor p53 is a very labile protein that undergoes Mdm2 and ubiquitin-dependent 26S proteasomal degradation (Haupt et al. 1997; Kubbutat et al. 1997).”
BackgroundSTRUCTURE AND FUNCTIONS OF THE 20S AND 26S PROTEASOMES
Coux, O., Tanaka, K., & Goldberg, A. L. (1996) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.65.070196.004101 · Cited by 2,438
Protein degradation and protection against misfolded or damaged proteins.
Goldberg, A. L. (2003) · Nature · doi:10.1038/nature02263 · Cited by 2,088
Glickman, M. H., Rubin, D. M., Coux, O., Wefes, I., Pfeifer, G., Cjeka, Z., Baumeister, W. P., Fried, V. A., & Finley, D. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81603-7 · Cited by 899
Proteasomes and their kin: proteases in the machine age
Pickart, C. M., & Cohen, R. E. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1336 · Cited by 735
O-GlcNAc Modification Is an Endogenous Inhibitor of the Proteasome
Zhang, F., Su, K., Yang, X., Bowe, D. B., Paterson, A. J., & Kudlow, J. E. (2003) · Cell · doi:10.1016/s0092-8674(03)00974-7 · Cited by 432
Research works printed but not linked: 3
- 10.1073/pnas.021558898 · DOI
- 1994, Mol. Cell. Biol., 14, 1997
- 2002, Cancer Res., 62, 3030
Cited by
Sorted by citations
Classification of Intrinsically Disordered Regions and Proteins
van der Lee, R., Buljan, M., Lang, B., Weatheritt, R. J., Daughdrill, G. W., Dunker, A. K., Fuxreiter, M., Gough, J., Gsponer, J., Jones, D. T., et al. (2014) · Chemical Reviews · doi:10.1021/cr400525m · Cited by 2,249
Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
Skrott, Z., Mistrik, M., Andersen, K. K., Friis, S., Majera, D., Gursky, J., Ozdian, T., Bartkova, J., Turi, Z., Moudry, P., et al. (2017) · Nature · doi:10.1038/nature25016 · Cited by 807
NAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790
“There is also evidence showing that a-synuclein competes with NAD+ for binding to the partially oxidized glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which co-localizes with a-synuclein in Lewy bodies in PD (Barinova et al., 2018).”
Introducing Protein Intrinsic Disorder
Habchi, J., Tompa, P., Longhi, S., & Uversky, V. N. (2014) · Chemical Reviews · doi:10.1021/cr400514h · Cited by 767
Dinkova‐Kostova, A. T., & Talalay, P. (2010) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2010.03.019 · Cited by 726
Metadata
- Authors
- Asher, G., Tsvetkov, P., Kahana, C., & Shaul, Y.
- Affiliations
- Weizmann Institute of Science (IL)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-02-01
- Volume
- 19
- Issue
- 3
- Pages
- 316-321
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC546509
- OpenAlex
- W2099952208
- Cited by
- 367
- References
- 24
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 8 · 2023: 8 · 2022: 14 · 2021: 23 · 2020: 17 · 2019: 21 · 2018: 16 · 2017: 26 · 2016: 15 · 2015: 13 · 2014: 23 · 2013: 11 · 2012: 18
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Academy of Sciences and Humanities
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- p53, p73, 20S proteasome, NQO1, NADH, tumor suppressor degradation, ionizing radiation response, protein degradation regulation
- MeSH terms
- Tumor Protein p73, Animals, Coenzymes, DNA-Binding Proteins, Humans, Nuclear Proteins, Protein Binding, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, NAD(P)H Dehydrogenase (Quinone), Tumor Suppressor Proteins, Ubiquitin, Protein Interaction Mapping, Proteasome Endopeptidase Complex
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
