ArticleCell death & disease2018
TSPY1 suppresses USP7-mediated p53 function and promotes spermatogonial proliferation.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond sex determination: the Y chromosome in male cancers.Nature reviews. Cancer · 2026Review
- Divergent Amplification of Y-Linked Dosage-Sensitive Genes Triggers Regulatory Mismatch Underlying Cattle-Yak Male Sterility.Biomolecules · 2026Article
- Structural insights into the interaction between testis-specific Y-encoded-like protein 5 and ubiquitin-specific protease 7.Protein science : a publication of the Protein Society · 2025Article
- Single-cell RNA-seq and pathological phenotype reveal the functional atlas and precise roles of Sox30 in testicular cell development and differentiation.Cell death & disease · 2025Article
- The lncRNA Gm8097 is associated with hypospermatogenesis.Clinical and experimental reproductive medicine · 2024Article
- The role of p53 in male infertility.Frontiers in endocrinology · 2024Review
- Insights into the Cellular Localization and Functional Properties of TSPYL5 Protein.International journal of molecular sciences · 2023Article
- SCML2 contributes to tumor cell resistance to DNA damage through regulating p53 and CHK1 stability.Cell death and differentiation · 2023Article
- Testis-Specific Protein Y-Encoded (TSPY) Is Required for Male Early Embryo Development inInternational journal of molecular sciences · 2023Article
- Hao-Fountain syndrome and genital disorders: report of a new possible association.Italian journal of pediatrics · 2022Article
- USP7 and SET9 Expression in The Oligospermic Human Semen: A Case-Control Study.International journal of fertility & sterility · 2022Article
- TRIP13 modulates protein deubiquitination and accelerates tumor development and progression of B cell malignancies.The Journal of clinical investigation · 2021Article
- Expression and Prognostic Characteristics of m6A RNA Methylation Regulators in Colon Cancer.International journal of molecular sciences · 2021Article
- Epigenetic modification-dependent androgen receptor occupancy facilitates the ectopic TSPY1 expression in prostate cancer cells.Cancer science · 2021Article
- Exploring the role of RALYL in Alzheimer's disease reserve by network-based approaches.Alzheimer's research & therapy · 2020Article
- Identification, functional prediction, and key lncRNA verification of cold stress-related lncRNAs in rats liver.Scientific reports · 2020Article
- Testis-specific protein, Y-linked 1 activates PI3K/AKT and RAS signaling pathways through suppressing IGFBP3 expression during tumor progression.Cancer science · 2019Article
- The Y-linked proto-oncogene TSPY contributes to poor prognosis of the male hepatocellular carcinoma patients by promoting the pro-oncogenic and suppressing the anti-oncogenic gene expression.Cell & bioscience · 2019Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Testis-specific protein Y-linked 1 (TSPY1) is expressed predominantly in adult human spermatogonia and functions in the process of spermatogenesis; however, our understanding of the underlying mechanism is limited. Here we observed that TSPY1, as an interacting partner of TSPY-like 5 (TSPYL5), enhanced the competitive binding of TSPYL5 to ubiquitin-specific peptidase 7 (USP7) in conjunction with p53. This activity, together with its promotion of TSPYL5 expression by acting as a transcription factor, resulted in increased p53 ubiquitylation. Moreover, TSPY1 could decrease the p53 level by inducing the degradation of ubiquitinated USP7. We demonstrated that the promotion of p53 degradation by TSPY1 influenced the activity of p53 target molecules (CDK1, p21, and BAX) to expedite the G2/M phase transition and decrease cell apoptosis, accelerating cell proliferation. Taken together, the observations reveal the significance of TSPY1 as a suppressor of USP7-mediated p53 function in inhibiting p53-dependent cell proliferation arrest. By simulating TSPY1 function in Tspy1-deficient spermatogonia derived from mouse testes, we found that TSPY1 could promote spermatogonial proliferation by decreasing the Usp7-modulated p53 level. The findings suggest an additional mechanism underlying the regulation of spermatogonial p53 function, indicating the significance of TSPY1 in germline homeostasis maintenance and the potential of TSPY1 in regulating human spermatogonial proliferation via the USP7-mediated p53 signaling pathway.
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