Disruption of HAUSP gene stabilizes p53.
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USP7 stabilizes Mdm2 by rapidly removing ubiquitin chains.
“While Mdm2 is also targeted for proteasomal degradation due its auto-polyubiquitination (Fang et al., 2000), USP7 is able to stabilize Mdm2 by rapidly removing these ubiquitin chains (Cummins et al., 2004; Li et al., 2004).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Cummins et al., 2004
One way USP7 inhibitors kill cancer cells is via stabilization of p53, resulting from degradation of Mdm2 in the absence of its USP7-mediated deubiquitination.
“One way through which this occurs is via the stabilization of p53, resulting from the degradation of Mdm2 in the absence of its USP7-mediated deubiquitination (Li et al., 2002, 2004; Cummins et al., 2004; Becker et al., 2008; Kategaya et al., 2017).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Cummins et al., 2004
The physiological consequence of Hausp loss is destabilization of Mdm2, which increases p53 levels and activity.
“Thus, the physiological consequence of Hausp loss is destabilization of Mdm2, which leads to increased p53 levels and activity (Cummins, et al., 2004; Li, et al., 2004).”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Cummins, et al., 2004
Hausp deubiquitinates Mdm2, allowing Mdm2 to keep p53 levels low.
“Hausp deubiquitinates Mdm2, which allows Mdm2 to functionally keep p53 levels low.”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Cummins, et al., 2004
Loss of Hausp by homologous recombination in human cell lines with wild-type p53 is incompatible with proliferation.
“Hausp loss by homologous recombination in human cell lines expressing wild-type p53 is incompatible with proliferation (Cummins, et al., 2004).”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Cummins, et al., 2004
Depletion of HAUSP in cells increases p53 levels.
“depletion of HAUSP in cells does not decrease p53 levels as predicted, but rather increases p53 levels”
From USP10 Regulates p53 Localization and Stability by Deubiquitinating p53 (2010) · cites this paper as Cummins et al., 2004
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“However, depletion of HAUSP in cells does not decrease p53 levels as predicted, but rather increases p53 levels (Cummins et al., 2004), apparently because of HAUSP’s ability to bind and deubiquitinate Mdm2 (Cummins et al.”
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“While Mdm2 is also targeted for proteasomal degradation due its auto-polyubiquitination (Fang et al., 2000), USP7 is able to stabilize Mdm2 by rapidly removing these ubiquitin chains (Cummins et al., 2004; Li et al., 2004).”
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- Authors
- Cummins, J. M., Rago, C., Kohli, M., Kinzler, K. W., Lengauer, C., & Vogelstein, B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Vogelstein, Bert
- Venue
- Nature
- Published
- 2004-04-01
- Volume
- 428
- Issue
- 6982
- Pages
- 1-2
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2000724093
- Cited by
- 379
- References
- 13
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 15 · 2023: 17 · 2022: 19 · 2021: 18 · 2020: 19 · 2019: 21 · 2018: 14 · 2017: 17 · 2016: 22 · 2015: 13 · 2014: 22 · 2013: 18 · 2012: 16
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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 › TGF-β signaling in diseases
- Keywords
- USP7, p53 stabilization, deubiquitination, ubiquitin-specific protease, p53 ubiquitination, MDM2, tumour suppressor, gene disruption, homologous recombination, protein stability
- MeSH terms
- Ubiquitin-Specific Peptidase 7, Alleles, Humans, Endopeptidases, Colorectal Neoplasms, Up-Regulation, Tumor Suppressor Protein p53, Gene Deletion, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin Thiolesterase, Cell Line, Tumor
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