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ISGylation: A Conserved Pathway in Mammalian Pregnancy

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Book cover Posttranslational Protein Modifications in the Reproductive System

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 759))

Abstract

Successful pregnancy includes remodeling and differentiation of the endometrium in response to sex steroid hormones, development of maternal immunotolerance to the implanting embryo, and modification of the local uterine environment by the embryo to suit its own needs. The major signal released by the ruminant conceptus during establishment of pregnancy is interferon-tau (IFNT) that stimulates the expression of many genes in the endometrium and ovary. One of these genes is called interferon stimulated gene 15 (ISG15), which encodes a ubiquitin homolog with a C-terminal Gly that becomes covalently attached to Lys residues on targeted proteins through an ATP-dependent multi-step enzymatic reaction called ISGylation. The conceptus-derived induction of endometrial ISGs also occurs in mouse and human deciduas and placenta, in response to pregnancy presumably through action of cytokines such as interleukins and type I IFN. Described herein is evidence to support the concept that ISGylation is a maternal response to the developing conceptus, implantation and placentation that is conserved across mammalian pregnancy. Although the precise role for ISG15 remains elusive during pregnancy, it is clear that up-regulation in response to pregnancy may impart a pre-emptive defense to infection or other environmental insults, and protection of the conceptus against inflammatory insults across species.

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Acknowledgments

This work was supported, in part, by the Traubert Professorship (TH) and grants from the National Institutes of Health, National Institute of Child Health and Development (HD032475 to TH and HD066297 to JP) and Office of the Director (OD010488 to JP), as well as the United States Department of Agriculture National Institute of Food and Agriculture (2011-67015-20067 and 2008-35204-04652) to TH.

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Authors and Affiliations

  1. Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, 3197 Rampart Road, Fort Collins, CO, 80521, USA

    Thomas R. Hansen

  2. Department of Animal Sciences, Center for Reproductive Biology, Washington State University, 1815 Ferdinand’s Lane, Pullman, WA, 99164, USA

    James K. Pru

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  1. Thomas R. Hansen
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  2. James K. Pru
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Correspondence to Thomas R. Hansen .

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Editors and Affiliations

  1. Division of Animal Sciences, and Departments of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri, USA

    Peter Sutovsky

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Hansen, T.R., Pru, J.K. (2014). ISGylation: A Conserved Pathway in Mammalian Pregnancy. In: Sutovsky, P. (eds) Posttranslational Protein Modifications in the Reproductive System. Advances in Experimental Medicine and Biology, vol 759. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0817-2_2

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  • DOI: https://doi.org/10.1007/978-1-4939-0817-2_2

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