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Nanos genes and their role in development and beyond

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Abstract

The hallmark of Nanos proteins is their typical (CCHC)2 zinc finger motif (zf-nanos). Animals have one to four nanos genes. For example, the fruit fly and demosponge have only one nanos gene, zebrafish and humans have three, and Fugu rubripes has four. Nanos genes are mainly known for their evolutionarily preserved role in germ cell survival and pluripotency. Nanos proteins have been reported to bind the C-terminal RNA-binding domain of Pumilio to form a post-transcriptional repressor complex. Several observations point to a link between the miRNA-mediated repression complex and the Nanos/Pumilio complex. Repression of the E2F3 oncogene product is, indeed, mediated by cooperation between the Nanos/Pumilio complex and miRNAs. Another important interaction partner of Nanos is the CCR4–NOT deadenylase complex. Besides the tissue-specific contribution of Nanos proteins to normal development, their ectopic expression has been observed in several cancer cell lines and various human cancers. An inverse correlation between the expression levels of human Nanos1 and Nanos3 and E-cadherin was observed in several cancer cell lines. Loss of E-cadherin, an important cell–cell adhesion protein, contributes to tumor invasion and metastasis. Overexpression of Nanos3 induces epithelial–mesenchymal transition in lung cancer cell lines partly by repressing E-cadherin. Other than some most interesting data from Nanos knockout mice, little is known about mammalian Nanos proteins, and further research is needed. In this review, we summarize the main roles of Nanos proteins and discuss the emerging concept of Nanos proteins as oncofetal antigens.

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Acknowledgements

We thank Dr. Amin Bredan for critical reading and careful editing of the manuscript, and our colleagues from Ghent University, VIB-UGent and the University of Reims (INSERM UMR-S 903) for helpful discussions. This work was supported by the Foundation against Cancer—Belgium, the Research Foundation—Flanders (FWO-Vlaanderen), and the Belgian Science Policy (Interuniversity Attraction Poles—Award IAP7/07). EDK has been a Ph.D. fellow of FWO-Vlaanderen.

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  1. VIB-UGent Center for Inflammation Research, Technologiepark 927, 9052, Ghent, Belgium

    Evi De Keuckelaere, Paco Hulpiau, Yvan Saeys & Frans van Roy

  2. Molecular Cell Biology Unit, Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium

    Evi De Keuckelaere, Paco Hulpiau & Frans van Roy

  3. Molecular and Cellular Oncology Laboratory, Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium

    Evi De Keuckelaere & Geert Berx

  4. Cancer Research Institute Ghent (CRIG), Ghent, Belgium

    Evi De Keuckelaere & Geert Berx

  5. Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Krijgslaan 281, S9, 9000, Ghent, Belgium

    Yvan Saeys

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  1. Evi De Keuckelaere
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De Keuckelaere, E., Hulpiau, P., Saeys, Y. et al. Nanos genes and their role in development and beyond. Cell. Mol. Life Sci. 75, 1929–1946 (2018). https://doi.org/10.1007/s00018-018-2766-3

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