Search for active endogenous retroviruses: identification and characterization of a HERV-E gene that is expressed in the pancreas and thyroid

Shiroma, Takashi; Sugimoto, Jun; Oda, Takaya; Jinno, Yoshihiro; Kanaya, Fuminori

doi:10.1007/s100380170012

Cited by 27 publications

(19 citation statements)

References 30 publications

(29 reference statements)

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“…The LTRs of HERV-E contain a promoter known to affect transcription of several cellular genes. Moreover, HERV-E transcripts have been seen in both normal and diseased tissues (52,65). To retrieve HERV-E(4-1) Env-encoding sequences, the same type of TBLASTN search that was initially made with ERV3 Env was also made with HERV-E Env.…”

Section: Downloaded Frommentioning

confidence: 99%

ERV3 and Related Sequences in Humans: Structure and RNA Expression

Andersson¹,

Yun²,

Sperber

et al. 2005

J Virol

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The ERV3 locus at chromosome 7q11 is a much studied human endogenous retroviral (HERV) sequence, owing to an env open reading frame (ORF) and placental RNA and protein expression. An analysis of the human genome demonstrated that ERV3 is one of a group of 41 highly related elements (ERV3-like HERVs) which use proline, isoleucine, or arginine tRNA in their primer binding sites. In addition to elements closely related to ERV3, the group included the previously known retinoic acid-inducible element, RRHERVI, also referred to as HERV15, but was separate from the related HERV-E elements. The ERV3-like elements are defective. The only element with an ORF among gag, pro, pol, and env genes was the env ORF of the original ERV3 locus. A search in dbEST revealed ERV3 RNA expression in placenta, skin, carcinoid tumor, and adrenal glands. Expression was also studied with newly developed real-time quantitative PCRs (QPCR) of ERV3 and HERV-E(4-1) env sequences. Results from a novel histone 3.3 RNA QPCR result served as the expression control. QPCR results for ERV3 were compatible with previously published results, with a stronger expression in adrenal gland and placenta than in 15 other human tissues. The expression of the envelope (env) of ERV3 at chromosome 7q11 was also studied by using stringent in situ hybridization. Expression was found in corpus luteum, testis, adrenal gland, Hassal's bodies in thymus, brown fat, pituitary gland, and epithelium of the lung. We conclude that ERV3 env is most strongly expressed in adrenal and sebaceous glands as well as in placenta.

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Section: Downloaded Frommentioning

confidence: 99%

ERV3 and Related Sequences in Humans: Structure and RNA Expression

Andersson¹,

Yun²,

Sperber

et al. 2005

J Virol

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“…In a broad assay on transcription profiles of HERV-H and HERV-W in different cell lines, the steroidresponsive breast cancer cell line T47D showed a high rate of HERV transcription; in particular, it was the only cell line with high expression of the HERV-F-RD pol gene ). Studies investigating HERVs in different tissue samples showed that adrenal cortex is a preferential site for ERV-9, which is expressed also in the medulla, HERV-R (ERV3) and HERV-E(4-1) (Katsumata et al, 1998;Andersson et al, 2002;Svensson et al, 2001); an HERV-E element mapping to 17q11 is preferentially expressed in thyroid and pancreas (Shiroma et al, 2001). Most noticeably, the retroviral envelope protein Env T in thyroid is a unique instance of specific expression in a healthy organ, and it may be associated with the hormone-producing status of the tissue (De Parseval et al, 2003).…”

Section: Endocrine Modulation Of Ervsmentioning

confidence: 99%

Factors regulating endogenous retroviral sequences in human and mouse

Taruscio

Mantovani

2004

Cytogenet Genome Res

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Endogenous retroviruses (ERVs) are stably integrated in the genome of vertebrates and inherited as Mendelian genes. The several human ERV (HERV) families and related elements represent up to 5–8% of the DNA of our species. ERVs may be involved in the regulation of adjacent genomic loci, especially promoting the tissue-specific expression of genes; some HERVs may have functional roles, e.g., coding for the placental fusogenic protein, syncytin. This paper reviews the growing evidence about factors that may modulate ERVs, including: cell and tissue types (with special attention to placenta and germ cells), processes related to differentiation and aging, cytokines, agents that disrupt cell functions (e.g., DNA hypomethylating agents) and steroids. Special attention is given to HERVs, due to their possible involvement in autoimmunity and reproduction, as well as altered expression in some cancer types; moreover, different HERV families may deserve specific attention, due to remarkable differences concerning, e.g., expression in tissues. A comparison with factors interacting with murine ERV-related sequences indicates that the mouse may be a useful model for studying some patterns of HERV regulation. Overall, the available evidence identifies the diverse, potential interactions with endogenous or exogenous factors as a promising field for investigating the roles of ERVs in physiology and disease.

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“…Nonetheless, retroviral genes are frequently expressed in normal and transformed human tissues. The function of these genes in normal human cell physiology is still unclear (32). So far, only the expression of the env gene of HERV-W is known to have a crucial function in normal organismal physiology, namely human trophoblast cell fusion and differentiation (5,12,23).…”

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confidence: 99%

Np9 Protein of Human Endogenous Retrovirus K Interacts with Ligand of Numb Protein X

Armbruester¹,

Sauter²,

Roemer³

et al. 2004

J Virol

121

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We have recently identified Np9 as a novel nuclear protein produced by the human endogenous retrovirus K and were able to document the exclusive presence of np9 transcript in tumors and transformed cells. With the aim of studying whether Np9 has a role in tumorigenesis, a systematic search for interacting proteins was performed. Here, we identify the RING-type E3 ubiquitin ligase LNX (ligand of Numb protein X) as an Np9-interacting partner. We furthermore show that the interaction involves N-and C-terminal domains of both proteins and can affect the subcellular localization of LNX. LNX has been reported to target the cell fate determinant and Notch antagonist Numb for proteasome-dependent degradation, thereby causing an increase in transactivational activity of Notch. We document that LNX-interacting Np9, like Numb, is unstable and degraded via the proteasome pathway and that ectopic Numb can stabilize recombinant Np9. Combined, these findings point to the possibility that Np9 affects tumorigenesis through the LNX/Numb/Notch pathway.Up to 8% of the human genome consists of retrovirusderived sequences (19). They are the result of numerous infections and subsequent integration of proviral elements into the germ line of human ancestors during the past 40 million years (2). Most of the recent human endogenous retrovirus (HERV) elements are defective due to the accumulation of mutations. Nonetheless, retroviral genes are frequently expressed in normal and transformed human tissues. The function of these genes in normal human cell physiology is still unclear (32). So far, only the expression of the env gene of HERV-W is known to have a crucial function in normal organismal physiology, namely human trophoblast cell fusion and differentiation (5,12,23). In contrast, retroviral gene expression has been linked to several human diseases, including tumorigenesis. In particular, expression of HERV-K seems to be strongly associated with transformation. Early hints pointing in this direction came from the observation that expression of the HERV-K proteins Gag and Env, as well as antibodies directed against these proteins, could be specifically detected in patients suffering from germ cell tumors (17,24,30,31). Other studies implicate a contribution of HERV-K10 gag RNA expression to the development of leukemia (9) or show that env as well as the expression of subgenomic env transcripts correlates with human breast cancer (35,36).It is unclear, at the present, how these proteins may support tumorigenesis. The Rev-like regulatory protein Rec (20,21)

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Search for active endogenous retroviruses: identification and characterization of a HERV-E gene that is expressed in the pancreas and thyroid

Cited by 27 publications

References 30 publications

ERV3 and Related Sequences in Humans: Structure and RNA Expression

ERV3 and Related Sequences in Humans: Structure and RNA Expression

Factors regulating endogenous retroviral sequences in human and mouse

Np9 Protein of Human Endogenous Retrovirus K Interacts with Ligand of Numb Protein X

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