Selective POTE Paralogs on Chromosome 2 are Expressed in Human Embryonic Stem Cells

Bera, Tapan K.; Fleur, Ashley Saint; Ha, D. Bui Dang; Yamada, Masanori; Lee, Yoomi; Lee, Byung Kook; Hahn, Yoonsoo; Kaufman, Dan S.; Pera, Martin F.; Pastan, Ira

doi:10.1089/scd.2007.0079

Cited by 19 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the role of many of these tumor-associated antigens in the disease process remains unclear, emerging evidence indicates that they appear to function in several important cellular processes such as transcriptional regulation, signal transduction, and cell growth [3]. Some also appear to function as putative proto-oncogenes [12,13] and are associated with maintaining the undifferentiated state of stem cells [14-17]. …”

Section: Introductionmentioning

confidence: 99%

Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

2013

View full text Add to dashboard Cite

BackgroundThe Cancer/Testis Antigens (CTAs) are a heterogeneous group of proteins whose expression is typically restricted to the testis. However, they are aberrantly expressed in most cancers that have been examined to date. Broadly speaking, the CTAs can be divided into two groups: the CTX antigens that are encoded by the X-linked genes and the non-X CT antigens that are encoded by the autosomes. Unlike the non-X CTAs, the CTX antigens form clusters of closely related gene families and their expression is frequently associated with advanced disease with poorer prognosis. Regardless however, the mechanism(s) underlying their selective derepression and stage-specific expression in cancer remain poorly understood, although promoter DNA demethylation is believed to be the major driver.MethodsHere, we report a systematic analysis of DNA methylation profiling data from various tissue types to elucidate the mechanism underlying the derepression of the CTAs in cancer. We analyzed the methylation profiles of 501 samples including sperm, several cancer types, and their corresponding normal somatic tissue types.ResultsWe found strong evidence for specific DNA hypomethylation of CTA promoters in the testis and cancer cells but not in their normal somatic counterparts. We also found that hypomethylation was clustered on the genome into domains that coincided with nuclear lamina-associated domains (LADs) and that these regions appeared to be insulated by CTCF sites. Interestingly, we did not observe any significant differences in the hypomethylation pattern between the CTAs without CpG islands and the CTAs with CpG islands in the proximal promoter.ConclusionOur results corroborate that widespread DNA hypomethylation appears to be the driver in the derepression of CTA expression in cancer and furthermore, demonstrate that these hypomethylated domains are associated with the nuclear lamina-associated domains (LADS). Taken together, our results suggest that wide-spread methylation changes in cancer are linked to derepression of germ-line-specific genes that is orchestrated by the three dimensional organization of the cancer genome.

show abstract

Section: Introductionmentioning

confidence: 99%

Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

2013

View full text Add to dashboard Cite

show abstract

“…Akt signaling ͉ coiled-coil motif ͉ insulin resistance ͉ hyperphagia ͉ POTE ancestor W e have been studying a family of primate-specific genes termed POTE, which are expressed in many cancers and embryonic stem cells, but only in a few normal adult tissues: prostate, ovary, and testis (1)(2)(3). The POTE genes entered the primate genome Ϸ20-40 Mya and appear to be under strong selective pressure because they evolved rapidly into 13 closely related paralogs located on 8 different chromosomes (4,5).…”

mentioning

confidence: 99%

A model for obesity and gigantism due to disruption of the Ankrd26 gene

Bera

Liu

Yamada

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Obesity is a major health hazard that is caused by a combination of genetic and behavioral factors. Several models of obesity have been described in mice that have defects in the production of peptide hormones, in the function of cell membrane receptors, or in a transcription factor required for neuronal cell development. We have been investigating the function of a family of genes (POTE and ANKRD26) that encode proteins that are associated with the inner aspect of the cell membrane and that contain both ankyrin repeats and spectrin helices, motifs known to interact with signaling proteins in the cell. To assess the function of ANKRD26, we prepared a mutant mouse with partial inactivation of the Ankrd26 gene. We find that the homozygous mutant mice develop extreme obesity, insulin resistance, and an increase in body size. The obesity is associated with hyperphagia with no reduction in energy expenditure and activity. The Ankrd26 protein is expressed in the arcuate and ventromedial nuclei within the hypothalamus and in the ependyma and the circumventricular organs that act as an interface between the peripheral circulation and the brain. In the enlarged hearts of the mutant mice, the levels of both phospho-Akt and mTOR were elevated. These results show that alterations in an unidentified gene can lead to obesity and identify a molecular target for the treatment of obesity.Akt signaling ͉ coiled-coil motif ͉ insulin resistance ͉ hyperphagia ͉ POTE ancestor W e have been studying a family of primate-specific genes termed POTE, which are expressed in many cancers and embryonic stem cells, but only in a few normal adult tissues: prostate, ovary, and testis (1-3). The POTE genes entered the primate genome Ϸ20-40 Mya and appear to be under strong selective pressure because they evolved rapidly into 13 closely related paralogs located on 8 different chromosomes (4, 5). They encode proteins that contain three domains: an amino-terminal cysteine-rich domain followed by ankyrin repeats and spectrinlike helices. Different paralogs contain different numbers of each of these components. In addition, an actin retroposon has been inserted in-frame in several family members, indicating that the gene is rapidly evolving in primates (6). The POTE genes evolved from a precursor gene, ANKRD26, which is located at 10p12.1 in humans and at chromosome 6 (qF1) in the mouse (5). The ANKRD26 gene also contains ankyrin repeats and spectrin helices but is missing the amino-terminal cysteine-rich domain of POTE (5).EST database analysis of both the human and mouse genomes (www.ncbi.nlm.nih.gov/UniGene/clust.cgi?ORG ϭ Hs&CID ϭ 361041) shows that ANKRD26 RNA is present in many normal tissues, but no function for this gene has been described. To gain information about a possible function for Ankrd26, we produced a mutant (MT) mouse in which the Ankrd26 gene is inactivated by insertion of a ␤-galactosidase cDNA. We report here that the homozygous Ankrd26 mutant mice have a very distinct phenotype consisting of extreme obesity and an increase in ...

show abstract

“…It has been reported that POTE was expressed in prostate, ovary, testis and placenta . The POTE 2 paralogs were reported to be predominantly expressed in undifferentiated human embryonic stem cells . Previous studies showed that several POTE paralogs (POTE‐2α, POTE‐2β, and POTE‐2γ) were predominantly expressed in prostate, breast, ovary, and lung cancers .…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of POTEG predicts poor prognosis in esophageal squamous cell carcinoma patients

Wang

Zhan

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

POTE ankyrin domain family, member G (poteg) belongs to POTE family. The POTE family is composed of many proteins which are very closely related and expressed in prostate, ovary, testis, and placenta. Some POTE paralogs are related with some cancers. Here we showed that down‐regulation of POTEG was detected in about 60% primary esophageal squamous cell carcinoma (ESCC) tumor tissues. Clinical association studies determined that POTEG down‐regulation was significantly correlated with tumor differentiation, lymph nodes metastasis and TNM staging. Kaplan‐Meier analysis determined that POTEG down‐regulation was associated with poorer clinical outcomes of ESCC patients (P = 0.026). Functional studies showed that POTEG overexpression could suppress tumor cell growth and metastasis capacity in vitro and in vivo. Molecular analyses revealed that POTEG downregulated CDKs, leading to subsequent inhibition of Rb phosphorylation, and consequently arrested Cell Cycle at G1/S Checkpoint. POTEG overexpression induced apoptosis by activating caspases and PARP, and regulating canonical mitochondrial apoptotic pathways. On the other side, POTEG inhibited epithelial‐mesenchymal transition and suppressed tumor cell metastasis. In conclusion, our study reveals a functionally important control mechanism of POTEG in esophageal cancer pathogenesis, suggesting potential use in the ESCC intervention and therapeutic strategies.

show abstract

Selective POTE Paralogs on Chromosome 2 are Expressed in Human Embryonic Stem Cells

Cited by 19 publications

References 18 publications

Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

A model for obesity and gigantism due to disruption of the Ankrd26 gene

Down‐regulation of POTEG predicts poor prognosis in esophageal squamous cell carcinoma patients

Contact Info

Product

Resources

About