USP7 deubiquitinates and stabilizes SIRT1.
Open accessAbstract
The NAD+‐dependent protein deacetylase silent information regulator 1 (SIRT1) targets multiple proteins for deacetylation, and it has been implicated in a variety of cellular pathways and human diseases. However, it remains unclear how the abundance of SIRT1 is regulated. Here, by mass spectrometry analysis of SIRT1‐containing protein complexes, we revealed that SIRT1 is physically associated with the ubiquitin‐specific protease USP7. Importantly, we found that USP7 cleaves K48‐linked polyubiquitin chains of SIRT1 and promotes SIRT1 stabilization. Accordingly, we demonstrated that treatment of cells with an enzymatic inhibitor of USP7 led to a decreased level of SIRT1 expression and accumulation of SIRT1 polyubiquitination. Collectively, our findings indicate that USP7 is a critical regulator of SIRT1 and provide a new pathway for the maintenance of SIRT1 abundance in cells. Anat Rec, 303:1337–1345, 2020. © 2019 American Association for Anatomy
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
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?
SIRT1 is deubiquitinated and stabilized by USP7.
“As SIRT1 was recently found to be deubiquitinated and stabilized by USP7, these findings suggest another way through which USP7 can regulate SUV39H1 activity and p53 transcription (Song et al., 2020).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Song et al., 2020
USP7 can regulate SUV39H1 activity and p53 transcription via SIRT1 stabilization.
“As SIRT1 was recently found to be deubiquitinated and stabilized by USP7, these findings suggest another way through which USP7 can regulate SUV39H1 activity and p53 transcription (Song et al., 2020).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Song et al., 2020
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · see citing works
Haberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,541 · see citing works
Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders
Falkenberg, K. J., & Johnstone, R. W. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4360 · Cited by 1,564 · cited 3× · see citing works
“Increasing experimental data show that the abnormal expression of HDACs is associated with a number of malignancies (Haberland et al., 2009; Falkenberg and Johnstone, 2014).”
BackgroundSIRT1 and other sirtuins in metabolism
Chang, H.-C., & Guarente, L. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.001 · Cited by 1,138 · see citing works
The increasing complexity of the ubiquitin code
Yau, R., & Rape, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3358 · Cited by 1,054 · see citing works
Kauppinen, A., Suuronen, T., Ojala, J. O., Kaarniranta, K., & Salminen, A. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.007 · Cited by 1,001 · see citing works
CBP/p300-mediated acetylation of histone H3 on lysine 56
Das, C., Lucia, M. S., Hansen, K. C., & Tyler, J. K. (2009) · Nature · doi:10.1038/nature07861 · Cited by 698 · see citing works
A dynamic role of HAUSP in the p53-Mdm2 pathway
Li, M., Brooks, C. L., Kon, N., & Gu, W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00157-1 · Cited by 679 · see citing works
Tumor Suppressor HIC1 Directly Regulates SIRT1 to Modulate p53-Dependent DNA-Damage Responses
Chen, W., Wang, D. H., Yen, R.-W. C., Luo, J., Gu, W. J., & Baylin, S. B. (2005) · Cell · doi:10.1016/j.cell.2005.08.011 · Cited by 649 · see citing works
The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.
Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002020 · Cited by 588 · see citing works
Sirtuins and NAD + in the Development and Treatment of Metabolic and Cardiovascular Diseases
Kane, A. E., & Sinclair, D. A. (2018) · Circulation Research · doi:10.1161/circresaha.118.312498 · Cited by 490 · see citing works
Structure of the p53 Binding Domain of HAUSP/USP7 Bound to Epstein-Barr Nuclear Antigen 1
Saridakis, V., Sheng, Y., Sarkari, F., Holowaty, M. N., Shire, K., Nguyen, T., Zhang, R. G., Liao, J. C. C., Lee, W., Edwards, A. M., et al. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.029 · Cited by 362 · see citing works
van Loosdregt, J., Fleskens, V., Fu, J., Brenkman, A., Bekker, C., Pals, C., Meerding, J., Berkers, C., Barbi, J., Gröne, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.018 · Cited by 325 · see citing works
SIRT1, Is It a Tumor Promoter or Tumor Suppressor?
Deng, C. (2009) · International Journal of Biological Sciences · doi:10.7150/ijbs.5.147 · Cited by 323 · see citing works
Molecular recognition of p53 and MDM2 by USP7/HAUSP.
Sheng, Y., Saridakis, V., Sarkari, F., Duan, S., Wu, T., Arrowsmith, C. H., & Frappier, L. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1067 · Cited by 315 · see citing works
Lin, Z., Yang, H., Kong, Q., Li, J., Lee, S.-M., Gao, B., Dong, H., Wei, J., Song, J., Zhang, D. D., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.03.024 · Cited by 315 · see citing works
Zhang, T., & Kraus, W. L. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.10.022 · Cited by 306 · see citing works
SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons
Dobbin, M. M., Madabhushi, R., Pan, L., Chen, Y., Kim, D., Gao, J., Ahanonu, B., Pao, P.-C., Qiu, Y., Zhao, Y., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3460 · Cited by 250 · see citing works
The Multifaceted Roles of USP7: New Therapeutic Opportunities
Nicholson, B., & Kumar, S. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9185-5 · Cited by 243 · see citing works
Lin, Z., & Fang, D. (2013) · Genes & Cancer · doi:10.1177/1947601912475079 · Cited by 241 · see citing works
Sirtuin regulation in aging and injury
Poulose, N., & Raju, R. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.017 · Cited by 236 · see citing works
Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis.
Wang, Q., Ma, S., Song, N., Li, X., Liu, L., Yang, S., Ding, X., Shan, L., Zhou, X., Su, D., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85747 · Cited by 206 · see citing works
Self-citationGao, Z., Zhang, J., Kheterpal, I., Kennedy, N., Davis, R. J., & Ye, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.228874 · Cited by 187 · see citing works
Emerging insights into HAUSP (USP7) in physiology, cancer and other diseases.
Bhattacharya, S., Chakraborty, D., Basu, M., & Ghosh, M. K. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0012-y · Cited by 162 · see citing works
SIRT1 and HIF1α signaling in metabolism and immune responses
Yu, Q., Lin, D., Li, Y., & Liu, G. (2018) · Cancer Letters · doi:10.1016/j.canlet.2017.12.035 · Cited by 157 · see citing works
Kinase and Histone Deacetylase Hybrid Inhibitors for Cancer Therapy
Luan, Y., Li, J., Bernatchez, J. A., & Li, R. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00189 · Cited by 148 · see citing works
Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1)
Liu, X., Wang, D., Zhao, Y., Tu, B., Zheng, Z., Wang, L., Wang, H., Gu, W. J., Roeder, R. G., & Zhu, W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019619108 · Cited by 137 · see citing works
Ubiquitin-specific protease 7 sustains DNA damage response and promotes cervical carcinogenesis
Su, D., Ma, S., Shan, L., Wang, Y., Wang, Y., Cao, C., Liu, B., Yang, C., Wang, L., Tian, S., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120518 · Cited by 114 · see citing works
Self-citationAn allosteric interaction links USP7 to deubiquitination and chromatin targeting of UHRF1.
Zhang, Z.-M., Rothbart, S. B., Allison, D. F., Cai, Q., Harrison, J. S., Li, L., Wang, Y., Strahl, B. D., Wang, G. G., & Song, J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.046 · Cited by 99 · see citing works
Role of SIRT1 in homologous recombination
Uhl, M., Csernok, A., DİLSİZ, S. A., Kreienberg, R., Wiesmüller, L., & Gatz, S. A. (2010) · DNA repair · doi:10.1016/j.dnarep.2009.12.020 · Cited by 90 · see citing works
Peng, L., Yuan, Z., Li, Y., Ling, H., Izumi, V., Fang, B., Fukasawa, K., Koomen, J. M., Chen, J., & Seto, E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.612796 · Cited by 65 · see citing works
Armour, S. M., Bennett, E. J., Braun, C. R., Zhang, X., McMahon, S. B., Gygi, S. P., Harper, J. W., & Sinclair, D. A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00971-12 · Cited by 62 · see citing works
SIRT1 regulates nuclear number and domain size in skeletal muscle fibers
Ross, J. A., Levy, Y., Svensson, K., Philp, A., Schenk, S., & Ochala, J. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26542 · Cited by 29 · see citing works
CHFR negatively regulates SIRT1 activity upon oxidative stress
Kim, M., Kwon, Y. E., Song, J. O., Bae, S. J., & Seol, J. H. (2016) · Scientific Reports · doi:10.1038/srep37578 · Cited by 24 · see citing works
Regulation of USP7/HAUSP in response to DNA damage: Yet another role for ATM
Khoronenkova, S. V., & Dianov, G. L. (2012) · Cell Cycle · doi:10.4161/cc.20800 · Cited by 9 · see citing works
Ubiquitin chains as second messengers
Cohen, P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2018.9 · Cited by 7 · see citing works
Flagged first, then by citations
4 of the 40 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- USP7 DEUBIQUITINATES AND STABILIZES SIRT1 1345 19328494, 2020, 5, Downloaded from https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/ar.24252 by Mount Vernon Nazarene University, Wiley Online Library on [28/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License · DOI
Cited by
Sorted by citations
USP7 Is a Master Regulator of Genome Stability
Valles, G. J., Bezsonova, I., Woodgate, R., & Ashton, N. W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00717 · Cited by 114 · see citing works
“As SIRT1 was recently found to be deubiquitinated and stabilized by USP7, these findings suggest another way through which USP7 can regulate SUV39H1 activity and p53 transcription (Song et al., 2020).”
BackgroundUSP7 - a crucial regulator of cancer hallmarks
Saha, G., Roy, S., Basu, M., & Ghosh, M. K. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188903 · Cited by 106 · see citing works
Tabrizi, F. B., Yarmohammadi, F., Hayes, A. W., & Karimi, G. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22946 · Cited by 40 · see citing works
USP7 manipulation by viral proteins
Bojagora, A., & Saridakis, V. (2020) · Virus Research · doi:10.1016/j.virusres.2020.198076 · Cited by 33 · see citing works
Long non-coding RNAs and microRNAs as crucial regulators in cardio-oncology
Nukala, S. B., Jousma, J., Cho, Y., Lee, W. H., & Ong, S. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00757-y · Cited by 32 · see citing works
Wang, M., Wei, R., Li, G., Bi, H.-L., Jia, Z., Zhang, M., Pang, M., Li, X., Ma, L., & Tang, Y. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215871 · Cited by 31 · see citing works
USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC
Wang, N., Li, T., Liu, W., Lin, J., Zhang, K., Li, Z., Huang, Y., Shi, Y., Xu, M., & Liu, X. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05706-2 · Cited by 31 · see citing works
Lee, S. H., Yang, J.-H., Park, U., Choi, H., Kim, Y. S., Yoon, B., Han, H.-J., Kim, H.-T., Um, S., & Kim, E.-J. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01012-1 · Cited by 29 · see citing works
Dong, X., Yang, C., Luo, Y., Dong, W., Xu, X., Wu, Y., & Wang, J. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1835900 · Cited by 26 · see citing works
The key vulnerabilities and therapeutic opportunities in the USP7-p53/MDM2 axis in cancer
Saha, G., & Ghosh, M. K. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2025.119908 · Cited by 17 · see citing works
Hou, D., Hu, Y., Tian, Y., Yu, D., & Yang, G. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149638 · Cited by 15 · see citing works
Lee, Y., Kim, S., & Surh, Y. (2022) · Journal of Cancer Prevention · doi:10.15430/jcp.2022.27.3.157 · Cited by 12 · see citing works
Protein Ubiquitination Modification in Pulmonary Fibrosis
Shen, J., Jiang, Y., Bu, W., Yu, M., Huang, R., Tang, C., Yang, Z., Gao, H., Su, L., Cheng, D., et al. (2025) · Comprehensive physiology · doi:10.1002/cph4.70013 · Cited by 10 · see citing works
Guerrini, V., Prideaux, B., Khan, R., Subbian, S., Wang, Y., Sadimin, E. T., Pawar, S., Ukey, R., Singer, E. A., Xue, C., et al. (2025) · The Journal of Immunology · doi:10.1093/jimmun/vkaf038 · Cited by 9 · see citing works
Cui, X., Li, C., He, S., & Li, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-04924-2 · Cited by 6 · see citing works
Shin, D. H., Choi, M., Han, C., & Kim, S. S. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01536-8 · Cited by 7 · see citing works
Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality
Guo, Q., Qin, H., Chen, Z., Zhang, W., Zheng, L., & Qin, T. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101311 · Cited by 3 · see citing works
Liu, Q., Zhang, J., Bai, J., & Liu, K. (2025) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-06244-7 · Cited by 2 · see citing works
Leng, Y., Liu, Z., Min, J., Ke, Q., Shao, Y., Lai, J., & Zhao, J. (2025) · Biochemical Genetics · doi:10.1007/s10528-024-10999-9 · Cited by 2 · see citing works
- Authors
- Song, N., Cao, C., Tian, S., Long, M., & Liu, L.
- Affiliations
- Tianjin Medical University (CN)
- Department of Clinical Laboratory The First Affiliated Hospital of Zhengzhou University, Key Clinical Laboratory Medicine of Henan Province Zhengzhou China
- Corresponding author
- Liu, Ling
- Venue
- The Anatomical Record
- Publisher
- Wiley
- Published
- 2019-10-21
- Volume
- 303
- Issue
- 5
- Pages
- 1337-1345
- ISSN
- 1932-8486 (ISSN-L)
- 1932-8494
- OpenAlex
- W2972886886
- Cited by
- 19
- References
- 40
- Citations by year
- 2025: 8 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Anatomical Record (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81872289)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- USP7, SIRT1, deubiquitination, protein stability, K48-linked polyubiquitin, protein-protein interaction, USP7 inhibitors, protein complexes
- MeSH terms
- Ubiquitin-Specific Peptidase 7, HeLa Cells, Humans, Tandem Mass Spectrometry, Ubiquitination, Sirtuin 1, MCF-7 Cells
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
