The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
TSPYL5 suppresses p53 levels and function by physical interaction with USP7.
Abstract
We have previously reported a gene expression signature that is a powerful predictor of poor clinical outcome in breast cancer. Among the seventy genes in this expression profile is a gene of unknown function: TSPYL5 (TSPY-like 5, also known as KIAA1750). TSPYL5 is located within a small region at chromosome 8q22 that is frequently amplified in breast cancer, which suggests that TSPYL5 has a causal role in breast oncogenesis. Here, we report that high TSPYL5 expression is an independent marker of poor outcome in breast cancer. Mass spectrometric analysis revealed that TSPYL5 interacts with ubiquitin-specific protease 7 (USP7; also known as herpesvirus-associated ubiquitin-specific protease; HAUSP). USP7 is the deubiquitylase for the p53 tumour suppressor and TSPYL5 reduces the activity of USP7 towards p53, resulting in increased p53 ubiquitylation. We demonstrate that TSPYL5 reduces p53 protein levels and inhibits activation of p53-target genes. Furthermore, expression of TSPYL5 overrides p53-dependent proliferation arrest and oncogene-induced senescence, and contributes to oncogenic transformation in multiple cell-based assays. Our data identify TSPYL5 as a suppressor of p53 function through its interaction with USP7.
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“TSPYL5 competitively binds to the USP7 TRAF-like domain, limiting USP7 substrate-binding (Epping et al., 2011).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Epping et al., 2011
In the citing paper
“TSPYL5 disrupts the p53-USP7 interaction, leading to increased polyubiquitination and degradation of p53.”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Epping et al., 2011
In the citing paper
“The p53-USP7 interaction is also negatively regulated by the TSPYL5 inhibitor protein (Epping et al., 2011).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Epping et al., 2011
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Bioconductor: open software development for computational biology and bioinformatics
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“The p53 tumour suppressor is essential for cell-cycle arrest and apoptosis after genotoxic stres”
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“We also expressed TSPYL5 in TIG3/16i cells, which are HDF-immortalized by hTERT and have a shRNA targeting CDKN2A”
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Metadata
- Authors
- Epping, M. T., Meijer, L. A. T., Krijgsman, O., Bos, J. L., Pandolfi, P. P., & Bernards, R.
- Affiliations
- The Netherlands Cancer Institute (NL)
- University Medical Center Utrecht (NL)
- Agendia (Netherlands) (NL)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Bernards, René
- Venue
- Nature Cell Biology
- Published
- 2010-12-19
- Volume
- 13
- Issue
- 1
- Pages
- 102-108
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2002052875
- Cited by
- 117
- References
- 32
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 6
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- TSPYL5, USP7, p53, deubiquitinase, protein-protein interaction, breast cancer, oncogene-induced senescence, proliferation arrest, oncogenic transformation, prognostic factors, tumour suppressor
- MeSH terms
- Ubiquitin-Specific Peptidase 7, Amino Acid Sequence, Animals, Breast Neoplasms, Cell Line, Chromosomes, Human, Pair 8, Female, Humans, Molecular Sequence Data, Nuclear Proteins, Prognosis, Protein Binding, Mass Spectrometry, Blotting, Western, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, RNA Interference, Ubiquitin Thiolesterase, Cell Line, Tumor, Immunoprecipitation, Kaplan-Meier Estimate, Ubiquitination
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