Identification of Differentially Expressed Nucleolar TGF-β1 Target (DENTT) in Human Lung Cancer Cells That Is a New Member of the TSPY/SET/NAP-1 Superfamily

Ozbun, Laurent; You, Liang; Kiang, Sharon C.; Angdisen, Jerry; Martı́nez, Alfredo; Jakowlew, Sonia B.

doi:10.1006/geno.2001.6505

Cited by 55 publications

(58 citation statements)

References 70 publications

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“…TSPX, on the other hand, was initially considered as a TSPY-like gene, termed TSPYlike 2. It has been independently isolated in various systems and has been designated as CDA1, DENTT and CASK-interacting nucleosome assembly protein (Chai et al, 2001;Ozbun et al, 2001;Wang et al, 2004a). Recent studies on the gene organization and encoded proteins showed that its gene structure is closely related to that of TSPY, including conservation of intron-exon junctions and sequences, particularly at SET/NAP domain, but with exceptions at their amino and C termini that encode a proline-rich and acidic domain, respectively (Delbridge et al, 2004;Lau et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…TSPY is normally expressed in male early germ cells during embryogenesis, and spermatogonia, spermatocytes and, to certain extent, the round spermatids, in adult testis (Zhang et al, 1992;Schnieders et al, 1996;Honecker et al, 2004;Lau, 2005, 2006), whereas TSPX is expressed ubiquitously in numerous cells/tissues (Ozbun et al, 2001(Ozbun et al, , 2003(Ozbun et al, , 2005Delbridge et al, 2004;Wang et al, 2004a;Lau et al, 2007). Such expression patterns suggest that TSPX could maintain a house-keeping function(s) in modulating cyclin B-CDK1 activities, and hence, cell-cycle progression, especially on G 2 /M transition, whereas TSPY has acquired various special functions pertaining to male stem germ cell proliferation and meiotic division.…”

Section: Discussionmentioning

confidence: 99%

“…These observations are in contrast to those of the SET oncoprotein and cell division autoantigen-1 (CDA1) (Chai et al, 2001;Canela et al, 2003). CDA1 and the differentially expressed nucleolar TGF-b1 target (DENTT) (Ozbun et al, 2001(Ozbun et al, , 2003 are isoforms encoded by the X-homologue of TSPY, which has recently been designated as TSPX (Delbridge et al, 2004). CDA1 differs from DENTT by 60 additional amino acids at its N terminus.…”

Section: Introductionmentioning

confidence: 94%

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TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

Lau

2008

Oncogene

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Testis-specific protein Y-encoded (TSPY) is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). TSPY and an X-homologue, TSPX, harbor a conserved domain, designated as SET/NAP domain, but differ at their C termini. Ectopic expression of TSPY accelerates cell proliferation by abbreviating the G 2 /M stage, whereas overexpression of TSPX retards cells at the same stage of the cell cycle. Previous studies demonstrated that the SET oncoprotein is capable of binding to cyclin B. Using various protein interaction techniques, we demonstrated that TSPY and TSPX indeed bind competitively to cyclin B at their SET/NAP domains in vitro and in vivo. TSPY colocalizes with cyclin B1 during the cell cycle, particularly on the mitotic spindles at metaphase. TSPY enhances while TSPX represses the cyclin B1-CDK1 phosphorylation activity. The inhibitory effect of TSPX on the cyclin B1-CDK1 complex has been mapped to its carboxyl acidic domain that is absent in TSPY, suggesting that TSPX could serve a normal function in modulating cell-cycle progression at the G 2 /M stage, whereas TSPY has acquired a specialized function in germ cell renewal and differentiation. Epigenetic dysregulation of TSPY in incompatible germ or somatic cells could promote cell proliferation and predispose susceptible cells to tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

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TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

Lau

2008

Oncogene

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“…We have previously reported that p21 Cip1 interacts with the SET protein, which was firstly identified as a CAN-fusion gene in an acute undifferentiated leukemia (von Lindern et al, 1992;Adachi et al, 1994). SET belongs to a family of proteins, which includes the yeast nucleosome assembly protein NAP-I (Kawase et al, 1996), MB20 (Shen et al, 2001), Cell Division Antigen-1 (Chai et al, 2001), nucleolar transforming growth factor-b1 target (Ozbun et al, 2001), supressor of presenilin-2 (Wen et al, 2000) and testis-specific protein Y-encoded (Vogel et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

et al. 2006

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We report here that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts in vitro and in vivo with the protein SET. This interaction is performed through the acidic domain of SET located at the carboxy terminal region. On analysing the functional relevance of SET-GAPDH interaction, we observed that GAPDH reverses in a dose-dependent manner, the inhibition of cyclin Bcdk1 activity produced by SET. Similarly to SET, GAPDH associates with cyclin B, suggesting that the regulation of cyclin B-cdk1 activity might be mediated not only by the interaction of GAPDH with SET but also with cyclin B. To analyse the putative role of GAPDH on cell cycle progression, HCT116 cells were transfected with a GAPDH expression vector. Results indicate that overexpression of GAPDH does not affect the timing of DNA replication but induces an increase in the number of mitosis, an advancement of the peak of cyclin B-cdk1 activity and an acceleration of cell cycle progression. All these results suggest that GAPDH might be involved in cell cycle regulation by modulating cyclin B-cdk1 activity.

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“…28 TSPYL2 (also known as CDA1, CINAP, or DENTT) facilitates chromatin assembly by binding to core histones in vitro and arrests cell growth. [29][30][31] Only a few studies have reported inactivation of the NAP-related protein in vitro. The downregulation of the TSPY gene in melanoma progression is caused by promoter hypermethylation.…”

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confidence: 99%

Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric cancers

Jung

Park

Bang

et al. 2008

Laboratory Investigation

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DNA methylation is crucial for normal development, but gene expression altered by DNA hypermethylation is often associated with human diseases, especially cancers. The gene TSPYL5, encoding testis-specific Y-like protein, was previously identified in microarray screens for genes induced by the inhibition of DNA methylation and histone deacetylation in glioma cell lines. The TSPYL5 showed a high frequency of DNA methylation-mediated silencing in both glioma cell lines and primary glial tumors. We now report that TSPYL5 is also inactivated by DNA methylation and could be a putative epigenetic target gene in gastric cancers. We found that the expression of TSPYL5 mRNA was frequently downregulated and inversely correlated with DNA methylation in seven out of nine gastric cancer cell lines. TSPYL5 mRNA expression was also restored after treating with a DNA methyltransferase inhibitor. In primary gastric tumors, methylation-specific PCR results in 23 of the 36 (63.9%) cases revealed that the hypermethylation at CpG islands of the TSPYL5 was detectable at a high frequency. Furthermore, TSPYL5 suppressed the growth of gastric cancer cells as demonstrated by a colony formation assay. Thus, strong associations between TSPYL5 expression and hypermethylation were observed, and aberrant methylation at a CpG island of TSPYL5 may play an important role in development of gastric cancers. Epigenetic events are heritable modifications that regulate gene expression and can contribute to cancer development. 1 In particular, changes in DNA methylation are among the most common molecular alterations in human neoplasia, because the hypermethylation of a tumor suppressor gene at a promoter can lead to transcriptional silencing and the loss of gene function. 1-4 Gastric cancer is one of the most common malignancies in the world. 5 The promoter hypermethylation of multiple tumor suppressor genes resulting in gene silencing has been recognized as an important mechanism in gastrointestinal carcinogenesis. [6][7][8][9][10][11][12][13][14][15] In a previous study, TSPYL5 was identified as one of the genes induced after treatment with DNA methylation and histone deacetylation inhibitors in glioma cell lines using microarray analysis. 16 The TSPYL5 showed a high frequency of DNA methylation-mediated silencing in both glioma cell lines and primary glial tumors. A human TSPYL5 encoding testis-specific Y-like protein 5 (TSPYL5) is located on chromosome 8q22.1, but its role in human cancer has not been fully understood. The TSPYL5 protein is a member of TSPYL family that includes TSPYL1, TSPYL2, TSPYL3, TSPYL4, and TSPYL6. TSPYL proteins are also members of the nucleosome assembly protein (NAP) superfamily. The TSPYLs show sequence homology to NAPs, which have a highly conserved domain (the NAP domain) of approximately 180 amino acids. 17,18 The NAP domain is known to be required and sufficient for histone binding. 19 Members of the NAP family of proteins were identified in different systems and were classified with the NAPs based on their sequenc...

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Identification of Differentially Expressed Nucleolar TGF-β1 Target (DENTT) in Human Lung Cancer Cells That Is a New Member of the TSPY/SET/NAP-1 Superfamily

Cited by 55 publications

References 70 publications

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

Glyceraldehyde 3-phosphate dehydrogenase is a SET-binding protein and regulates cyclin B-cdk1 activity

Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric cancers

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