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      Proteolysis in Reproduction: Lessons From Gene-Modified Organism Studies

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          Abstract

          The physiological roles of proteolysis are not limited to degrading unnecessary proteins. Proteolysis plays pivotal roles in various biological processes through cleaving peptide bonds to activate and inactivate proteins including enzymes, transcription factors, and receptors. As a wide range of cellular processes is regulated by proteolysis, abnormalities or dysregulation of such proteolytic processes therefore often cause diseases. Recent genetic studies have clarified the inclusion of proteases and protease inhibitors in various reproductive processes such as development of gonads, generation and activation of gametes, and physical interaction between gametes in various species including yeast, animals, and plants. Such studies not only clarify proteolysis-related factors but the biological processes regulated by proteolysis for successful reproduction. Here the physiological roles of proteases and proteolysis in reproduction will be reviewed based on findings using gene-modified organisms.

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          Most cited references208

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          Saccharomyces Genome Database: the genomics resource of budding yeast

          The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use.
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            Essential role of Plzf in maintenance of spermatogonial stem cells.

            Little is known of the molecular mechanisms whereby spermatogonia, mitotic germ cells of the testis, self-renew and differentiate into sperm. Here we show that Zfp145, encoding the transcriptional repressor Plzf, has a crucial role in spermatogenesis. Zfp145 expression was restricted to gonocytes and undifferentiated spermatogonia and was absent in tubules of W/W(v) mutants that lack these cells. Mice lacking Zfp145 underwent a progressive loss of spermatogonia with age, associated with increases in apoptosis and subsequent loss of tubule structure but without overt differentiation defects or loss of the supporting Sertoli cells. Spermatogonial transplantation experiments revealed a depletion of spermatogonial stem cells in the adult. Microarray analysis of isolated spermatogonia from Zfp145-null mice before testis degeneration showed alterations in the expression profile of genes associated with spermatogenesis. These results identify Plzf as a spermatogonia-specific transcription factor in the testis that is required to regulate self-renewal and maintenance of the stem cell pool.
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              Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast.

              In eukaryotic cells, replicated DNA strands remain physically connected until their segregation to opposite poles of the cell during anaphase. This "sister chromatid cohesion" is essential for the alignment of chromosomes on the mitotic spindle during metaphase. Cohesion depends on the multisubunit cohesin complex, which possibly forms the physical bridges connecting sisters. Proteolytic cleavage of cohesin's Sccl subunit at the metaphase to anaphase transition is essential for sister chromatid separation and depends on a conserved protein called separin. We show here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro. Cleavage of Sccl in metaphase arrested cells is sufficient to trigger the separation of sister chromatids and their segregation to opposite cell poles.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                04 May 2022
                2022
                : 13
                : 876370
                Affiliations
                [1] 1 Research Institute for Microbial Diseases, Osaka University , Suita, Japan
                [2] 2 PRESTO, Japan Science and Technology Agency , Kawaguchi, Japan
                [3] 3 The Institute of Medical Science, The University of Tokyo , Tokyo, Japan
                [4] 4 CREST, Japan Science and Technology Agency , Kawaguchi, Japan
                Author notes

                Edited by: Erwin Goldberg, Northwestern University, United States

                Reviewed by: Toshinobu Tokumoto, Shizuoka University, Japan; Martine Culty, University of Southern California, United States

                *Correspondence: Daiji Kiyozumi, kiyozumi@ 123456biken.osaka-u.ac.jp ; Masahito Ikawa, ikawa@ 123456biken.osaka-u.ac.jp

                This article was submitted to Reproduction, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2022.876370
                9114714
                35600599
                e9f6a0c7-2751-461f-be8d-4000040fdd00
                Copyright © 2022 Kiyozumi and Ikawa

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 February 2022
                : 28 March 2022
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 208, Pages: 19, Words: 8411
                Funding
                Funded by: Japan Society for the Promotion of Science, doi 10.13039/501100001691;
                Award ID: JP21H00231
                Funded by: Japan Science and Technology Agency, doi 10.13039/501100002241;
                Award ID: 21460710
                Funded by: National Institutes of Health, doi 10.13039/100000002;
                Award ID: R01HD088412
                Funded by: Bill and Melinda Gates Institute for Population and Reproductive Health, doi 10.13039/100009053;
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                protease,fertilization,proteolysis,protease inhibitor,pseudoprotease,gene-modified animal models,ubiquitin-proteasome system,sperm maturation

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