ArticleHuman molecular genetics2017
The Y-located proto-oncogene TSPY exacerbates and its X-homologue TSPX inhibits transactivation functions of androgen receptor and its constitutively active variants.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Beyond sex determination: the Y chromosome in male cancers.Nature reviews. Cancer · 2026Review
- The TSPY gene and the loss of Y chromosome predisposition to cancers.Cell & bioscience · 2026Article
- TSPY-like 2, Beyond the Histone Chaperone Role.Biomolecules · 2026Review
- Y-chromosome alteration and its impact on cancer progression and metastasis.Cellular & molecular biology letters · 2025Review
- Gender and sex interactions are intrinsic components of cancer phenotypes.Nature reviews. Cancer · 2025Review
- The human testis-specific protein Y-linked (TSPY) is a male-specific cancer-testis antigen capable of eliciting significant immune responses and elimination of positive tumor cells in hepatocellular carcinoma.Cell & bioscience · 2025Article
- Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities.Nature reviews. Cancer · 2025Review
- Article
- Genetic Analysis of 27 Y-STR Haplotypes in 11 Iranian Ethnic Groups.Archives of Iranian medicine · 2024Article
- Y chromosome is moving out of sex determination shadow.Cell & bioscience · 2022Review
- Repetitive DNA Sequences in the Human Y Chromosome and Male Infertility.Frontiers in cell and developmental biology · 2022Review
- Update on genetic screening and treatment for infertile men with genetic disorders in the era of assisted reproductive technology.Clinical and experimental reproductive medicine · 2021Article
- Epigenetic modification-dependent androgen receptor occupancy facilitates the ectopic TSPY1 expression in prostate cancer cells.Cancer science · 2021Article
- Analysis of novel enzalutamide-resistant cells: upregulation of testis-specific Y-encoded protein gene promotes the expression of androgen receptor splicing variant 7.Translational cancer research · 2020Article
- Potential dual functional roles of the Y-linked RBMY in hepatocarcinogenesis.Cancer science · 2020Article
- Y chromosome in health and diseases.Cell & bioscience · 2020Review
- Review
- Lost in translational biology: Understanding sex differences to inform studies of diseases of the nervous system.Brain research · 2019Review
- Testis-specific protein, Y-linked 1 activates PI3K/AKT and RAS signaling pathways through suppressing IGFBP3 expression during tumor progression.Cancer science · 2019Article
- The X-linked tumor suppressor TSPX downregulates cancer-drivers/oncogenes in prostate cancer in a C-terminal acidic domain dependent manner.Oncotarget · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The gonadoblastoma gene, testis-specific protein Y-encoded (TSPY), on the Y chromosome and its X-homologue, TSPX, are cell cycle regulators and function as a proto-oncogene and a tumor suppressor respectively in human oncogenesis. TSPY and TSPX competitively bind to the androgen receptor (AR) and AR variants, such as AR-V7, at their conserved SET/NAP domain, and exacerbate and repress the transactivation of the AR/AR-V7 target genes in ligand dependent and independent manners respectively. The inhibitory domain has been mapped to the carboxyl acidic domain of TSPX, truncation of which renders TSPX to be stimulatory while its transposition to the C-terminus of TSPY results in an inhibitory hybrid protein. TSPY and TSPX co-localize with the endogenous AR, in the presence of ligand, on the promoters and differentially regulate the expression of the endogenous AR target genes in the androgen-responsive LNCaP prostate cancer cells. Transcriptome analysis shows that TSPY and TSPX expressions differentially affect significant numbers of canonical pathways, upstream regulators and cellular functions. Significantly, among the common ones, TSPY activates and TSPX inhibits numerous growth-related and oncogenic canonical pathways and cellular functions in the respective cell populations. Hence, TSPY and TSPX exert opposing effects on the transactivation functions of AR and AR-Vs important for various physiological and disease processes sensitive to male sex hormone actions, thereby not only affecting the pathogenesis of male-specific prostate cancer but also likely contributing to sex differences in the health and diseases of man.
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Registered trials
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