The viral oncogene Np9 acts as a critical molecular switch for co-activating β-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells

Chen, T; Meng, Zhipeng; Gan, Yichao; Wang, X; Xu, Fei; Gu, Ye; Xu, Xiao; Tang, Jinyu; Zhou, Honggeng; Zhang, Xiaobo; Gan, Xu; Ness, Carl Van; Xu, Guihua; Huang, Lu; Fang, Yiqi; Wu, Jia; Zheng, Shu; Jin, Jiaxin; Huang, Wendong; Xu, Rui‐hua

doi:10.1038/leu.2013.8

Cited by 110 publications

(123 citation statements)

References 35 publications

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“…A growing number of large-scale sequencing studies have reported detection of somatic TE insertions in some types of human cancers, and potential roles for such new insertions in malignancy are being actively investigated (49)(50)(51)(52). Other studies have investigated potential roles for human ERV-encoded proteins in cancer (53)(54)(55) or reported general transcriptional up-regulation of ERVs or L1s in various malignancies (for reviews see refs. 56 and 57).…”

Section: Activation Of Te-gene Chimeras Is Associated With Epigeneticmentioning

confidence: 99%

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Lock

Rebollo

Miceli-Royer

et al. 2014

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

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Significance Sequences derived from transposable elements (TEs) are abundant in the human genome and can influence gene expression. In normal cells, most TEs are silenced by epigenetic mechanisms such as DNA methylation but, in cancer, normally dormant TEs can become active. We hypothesized that cancer-specific release of epigenetic suppression of TEs could result in gene expression perturbations, which could promote oncogenesis. Using a bioinformatics method, we identified many genes expressed in diffuse large B-cell lymphoma (DLBCL) via activation of TE promoters. Further analysis of one, FABP7 , showed it was expressed in some DLBCL samples through use of a TE promoter. The TE-driven FABP7 transcript encodes a novel isoform of the protein, which is required for optimal DLBCL cell line proliferation.

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Section: Activation Of Te-gene Chimeras Is Associated With Epigeneticmentioning

confidence: 99%

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Lock

Rebollo

Miceli-Royer

et al. 2014

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

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“…In human leukemia cells, Np9 protein level is substantially higher than that in normal cells, e.g., in normal hematopoietic stem cells. Np9 may act by activating ERK, AKT and Notch1 signaling pathways and through the upregulation of b-catenin, essential for survival of leukemia stem cells [212]. Another group of researchers found that Np9 may directly interact with the RING-type E3 ubiquitin ligase LNX protein [59].…”

Section: Cancermentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

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Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

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“…HERV-K (HML-2), the youngest family of ERVs in the human genome, has been extensively investigated for potential pathogenicity and some evidence suggests that the HERV-K-encoded accessory proteins Rec and Np9 have a carcinogenic role, particularly in germ cell tumors, but also in some other cancers (26,122,123). As ongoing retrotranspositional activity of ERVs is low or nonexistent in modern humans (46), it is not surprising that no instances of activation of oncogenes via new ERV insertions have been found in human malignancy.…”

Section: Pathogenic Effects Of Ervs and Related Sequences On The Hostmentioning

confidence: 99%

Mammalian Endogenous Retroviruses

Mager

Stoye²

2015

Microbiol Spectr

171

103

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Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles.

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The viral oncogene Np9 acts as a critical molecular switch for co-activating β-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells

Cited by 110 publications

References 35 publications

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Molecular functions of human endogenous retroviruses in health and disease

Mammalian Endogenous Retroviruses

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