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The TSPY Gene Family
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The TSPY Gene Family

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 July 2010) | Viewed by 47698

Special Issue Editor

Prof. Dr. Yun-Fai Chris Lau

E-Mail Website
Guest Editor
Laboratory of Cell and Developmental Genetics, Department of Medicine, VA Medical Center, University of California, San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA
Interests: Y chromosome genes; sex determination; sexual dimorphisms; developmental genetics; cell cycle; male-specific cancers

Special Issue Information

Dear Colleagues,

The testis-specific protein Y encoded (TSPY) gene is one of the first genes identified on the human Y chromosome. TSPY is a tandemly repeated and evolutionarily conserved gene on the mammalian Y chromosome. Importantly it is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY), responsible for predisposing dysgenetic gonads of XY sex-reversed and intersex patients for gonadoblastoma development. TSPY encodes a variety of polymorphic proteins harboring a conserved domain, termed SET/NAP domain found in the SET oncoprotein and nucleosome assembly protein 1.
Various studies show that TSPY is a founding member of a family of proteins, termed TSPY-like proteins harboring the same homologous SET/NAP domain. In particular, an X-located single-copy homologue, designed recently as TSPX (and other designations), shows similar gene organization and protein structure. Interestingly TSPY and TSPX possess contrasting properties and have been considered to be a proto-oncogene and tumor suppressor respectively. TSPY and TSPY-like genes serve diverse functions, including cell cycle regulation, transcription regulation, neurotransmission, meiotic division, tumor suppression and promotion. Mutations and/or dysregulation of TSPY gene family members are associated with various human diseases, including infertility, cancers, diabetes, and neural dysfunctions.
The purpose of this special issue of Genes is to summarize the current advances in research on TSPY gene family by various established investigators in the field, focusing on the evolution, genomic organization, protein structures, biological functions in normal development and physiology, and pathogeneses of various diseases.

Prof. Dr. Yun-Fai Chris Lau
Guest Editor

Keywords

  • testis-specific protein Y-encoded (TSPY)
  • TSPY-like proteins
  • male meiosis
  • gonadoblastoma oncogene
  • germ cell tumor stem cells
  • cell cycle regulation
  • transcription regulation
  • neural functions
  • tumor suppressor
  • sexual dimorphisms

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Published Papers (5 papers)

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Research

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410 KiB  
Article
Expression of the Y-Encoded TSPY is Associated with Progression of Prostate Cancer
by Tatsuo Kido, Shingo Hatakeyama, Chikara Ohyama and Yun-Fai Chris Lau
Genes 2010, 1(2), 283-293; https://doi.org/10.3390/genes1020283 - 14 Sep 2010
Cited by 19 | Viewed by 7781
Abstract
TSPY is a Y-encoded gene that is expressed in normal testicular germ cells and various cancer types including germ cell tumor, melanoma, hepatocellular carcinoma, and prostate cancer. Currently, the correlation between TSPY expression and oncogenic development has not been established, particularly in somatic [...] Read more.
TSPY is a Y-encoded gene that is expressed in normal testicular germ cells and various cancer types including germ cell tumor, melanoma, hepatocellular carcinoma, and prostate cancer. Currently, the correlation between TSPY expression and oncogenic development has not been established, particularly in somatic cancers. To establish such correlation, we analyzed the expression of TSPY, in reference to its interactive oncoprotein, EEF1A, tumor biomarker, AMACR, and normal basal cell biomarker, p63, in 41 cases of clinical prostate cancers (CPCa), 17 cases of latent prostate cancers (LPCa), and 19 cases of non-cancerous prostate (control) by immunohistochemistry. Our results show that TSPY was detected more frequently (78%) in the clinical prostate cancer specimens than those of latent prostate cancer (47%) and control (50%). In the latent cancer group, the levels of TSPY expression could be correlated with increasing Gleason grades. TSPY expression was detected in seven out of nine high-grade latent cancer samples (Gleason 7 and more). The expression of the TSPY binding partner EEF1A was detectable in all prostate specimens, but the levels were higher in cancer cells in clinical and latent prostate cancer specimens than normal prostatic cells. These observations suggest that expressions of TSPY and its binding partner EEF1A are associated with the development and progression of prostate cancer. Full article
(This article belongs to the Special Issue The TSPY Gene Family)
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Review

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311 KiB  
Review
An Exceptional Gene: Evolution of the TSPY Gene Family in Humans and Other Great Apes
by Yali Xue and Chris Tyler-Smith
Genes 2011, 2(1), 36-47; https://doi.org/10.3390/genes2010036 - 10 Jan 2011
Cited by 17 | Viewed by 8508
Abstract
The TSPY gene stands out from all other human protein-coding genes because of its high copy number and tandemly-repeated organization. Here, we review its evolutionary history in great apes in order to assess whether these unusual properties are more likely to result from [...] Read more.
The TSPY gene stands out from all other human protein-coding genes because of its high copy number and tandemly-repeated organization. Here, we review its evolutionary history in great apes in order to assess whether these unusual properties are more likely to result from a relaxation of constraint or an unusual functional role. Detailed comparisons with chimpanzee are possible because a finished sequence of the chimpanzee Y chromosome is available, together with more limited data from other apes. These comparisons suggest that the human-chimpanzee ancestral Y chromosome carried a tandem array of TSPY genes which expanded on the human lineage while undergoing multiple duplication events followed by pseudogene formation on the chimpanzee lineage. The protein coding region is the most highly conserved of the multi-copy Y genes in human-chimpanzee comparisons, and the analysis of the dN/dS ratio indicates that TSPY is evolutionarily highly constrained, but may have experienced positive selection after the human-chimpanzee split. We therefore conclude that the exceptionally high copy number in humans is most likely due to a human-specific but unknown functional role, possibly involving rapid production of a large amount of TSPY protein at some stage during spermatogenesis. Full article
(This article belongs to the Special Issue The TSPY Gene Family)
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208 KiB  
Review
Role of Cell Division Autoantigen 1 (CDA1) in Cell Proliferation and Fibrosis
by Ban-Hock Toh, Yugang Tu, Zemin Cao, Mark E. Cooper and Zhonglin Chai
Genes 2010, 1(3), 335-348; https://doi.org/10.3390/genes1030335 - 30 Sep 2010
Cited by 10 | Viewed by 9435
Abstract
Cell Division Autoantigen 1 (CDA1) was discovered following screening a human expression library with serum from a patient with Discoid Lupus Erythematosus. CDA1, encoded by TSPYL2 on the X chromosome, shares anti-proliferative and pro‑fibrotic properties with TGF-b. It inhibits cell growth through p53, [...] Read more.
Cell Division Autoantigen 1 (CDA1) was discovered following screening a human expression library with serum from a patient with Discoid Lupus Erythematosus. CDA1, encoded by TSPYL2 on the X chromosome, shares anti-proliferative and pro‑fibrotic properties with TGF-b. It inhibits cell growth through p53, pERK1/2 and p21‑mediated pathways and is implicated in tumorigenesis and the DNA damage response. Its pro-fibrotic property is mediated through cross-talk with TGF-b that results in upregulation of extracellular matrix proteins. The latter properties have identified a key role for CDA1 in diabetes associated atherosclerosis. These dual properties place CDA1 as an attractive molecular target for treating tumors and vascular fibrosis including atherosclerosis and other vascular disorders associated with enhanced TGF-β action and tissue scarring. Full article
(This article belongs to the Special Issue The TSPY Gene Family)
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103 KiB  
Review
TSPY and Male Fertility
by Csilla Krausz, Claudia Giachini and Gianni Forti
Genes 2010, 1(2), 308-316; https://doi.org/10.3390/genes1020308 - 21 Sep 2010
Cited by 26 | Viewed by 8576
Abstract
Spermatogenesis requires the concerted action of thousands of genes, all contributing to its efficiency to a different extent. The Y chromosome contains several testis-specific genes and among them the AZF region genes on the Yq and the TSPY1 array on the Yp are [...] Read more.
Spermatogenesis requires the concerted action of thousands of genes, all contributing to its efficiency to a different extent. The Y chromosome contains several testis-specific genes and among them the AZF region genes on the Yq and the TSPY1 array on the Yp are the most relevant candidates for spermatogenic function. TSPY1 was originally described as the putative gene for the gonadoblastoma locus on the Y (GBY) chromosome. Besides its oncogenic properties, expression analyses in the testis and in vitro and in vivo studies all converge on a physiological involvement of the TSPY1 protein in spermatogenesis as a pro-proliferative factor. The majority of TSPY1 copies are arranged in 20.4 kb of tandemly repeated units, with different copy numbers among individuals. Our recent study addressing the role of TSPY1 copy number variation in spermatogenesis reported that TSPY1 copy number influences spermatogenic efficiency and is positively correlated with sperm count. This finding provides further evidence for a role of TSPY1 in testicular germ cell proliferation and stimulates future research aimed at evaluating the relationship between the copy number and the protein expression level of the TSPY1 gene. Full article
(This article belongs to the Special Issue The TSPY Gene Family)
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862 KiB  
Review
Transgenic Mouse Studies to Understand the Regulation, Expression and Function of the Testis-Specific Protein Y-Encoded (TSPY) Gene
by Stephanie Schubert and Jörg Schmidtke
Genes 2010, 1(2), 244-262; https://doi.org/10.3390/genes1020244 - 18 Aug 2010
Cited by 4 | Viewed by 9351
Abstract
The TSPY gene, which encodes the testis-specific protein, Y-encoded, was first discovered and characterized in humans, but orthologous genes were subsequently identified on the Y chromosome of many other placental mammals. TSPY is expressed in the testis and [...] Read more.
The TSPY gene, which encodes the testis-specific protein, Y-encoded, was first discovered and characterized in humans, but orthologous genes were subsequently identified on the Y chromosome of many other placental mammals. TSPY is expressed in the testis and to a much lesser extent in the prostate gland, and it is assumed that TSPY serves function in spermatogonial proliferation and/or differentiation. It is further supposed that TSPY is involved in male infertility and exerts oncogenic effects in gonadal and prostate tumor formation. As a member of the TSPY/SET/NAP protein family, TSPY is able to bind cyclin B types, and stimulates the cyclin B1-CDK1 kinase activity, thereby accelerating the G2/M phase transition of the cell cycle of target cells. Because the laboratory mouse carries only a nonfunctional Y-chromosomal Tspy-ps pseudogene, a knockout mouse model for functional research analyses is not a feasible approach. In the last decade, three classical transgenic mouse models have been developed to contribute to our understanding of TSPY regulation, expression and function. The different transgenic mouse approaches and their relevance for studying TSPY regulation, expression and function are discussed in this review. Full article
(This article belongs to the Special Issue The TSPY Gene Family)
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