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Degradation of the Separase-cleaved Rec8, a Meiotic Cohesin Subunit, by the N-end Rule Pathway

Liu, Yu-Jiao and Liu, Chao and Chang, ZeNan and Wadas, Brandon and Brower, Christopher S. and Song, Zhen-Hua and Xu, Zhi-Liang and Shang, Yong-Liang and Liu, Wei-Xiao and Wang, Li-Na and Dong, Wen and Varshavsky, Alexander and Hu, Rong-Gui and Li, Wei (2016) Degradation of the Separase-cleaved Rec8, a Meiotic Cohesin Subunit, by the N-end Rule Pathway. Journal of Biological Chemistry, 291 (14). pp. 7426-7438. ISSN 0021-9258. PMCID PMC4817174. http://resolver.caltech.edu/CaltechAUTHORS:20160218-082640962

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Abstract

The Ate1 arginyltransferase (R-transferase) is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. Ate1 arginylates N-terminal Asp, Glu, or (oxidized) Cys. The resulting N-terminal Arg is recognized by ubiquitin ligases of the N-end rule pathway. In the yeast Saccharomyces cerevisiae, the separase-mediated cleavage of the Scc1/Rad21/Mcd1 cohesin subunit generates a C-terminal fragment that bears N-terminal Arg and is destroyed by the N-end rule pathway without a requirement for arginylation. In contrast, the separase-mediated cleavage of Rec8, the mammalian meiotic cohesin subunit, yields a fragment bearing N-terminal Glu, a substrate of the Ate1 R-transferase. Here we constructed and used a germ cell-confined Ate1−/− mouse strain to analyze the separase-generated C-terminal fragment of Rec8. We show that this fragment is a short-lived N-end rule substrate, that its degradation requires N-terminal arginylation, and that male Ate1−/− mice are nearly infertile, due to massive apoptotic death of Ate1−/− spermatocytes during the metaphase of meiosis I. These effects of Ate1 ablation are inferred to be caused, at least in part, by the failure to destroy the C-terminal fragment of Rec8 in the absence of N-terminal arginylation.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1074/jbc.M116.714964DOIArticle
http://www.jbc.org/content/291/14/7426PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817174/PubMed CentralArticle
ORCID:
AuthorORCID
Varshavsky, Alexander0000-0002-4011-258X
Additional Information:© 2016 The American Society for Biochemistry and Molecular Biology. Received January 9, 2016. Accepted February 8, 2016. First Published on February 8, 2016. We are grateful to Qingyuan Sun (Institute of Zoology, Chinese Academy of Sciences) for anti-Rec8 antibody. This work was supported by National Natural Science Foundation of China Grants 31171374 and 31471277 and Major Basic Research Program Grant 2012CB944404 (to W. L.) and by National Institutes of Health Grants R01-DK039520 and R01-GM031530 (to A. V.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funders:
Funding AgencyGrant Number
National Natural Science Foundation of China31171374
National Natural Science Foundation of China31471277
National Natural Science Foundation of China2012CB944404
NIHR01-DK039520
NIHR01-GM031530
PubMed Central ID:PMC4817174
Record Number:CaltechAUTHORS:20160218-082640962
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160218-082640962
Official Citation:Yu-Jiao Liu, Chao Liu, ZeNan Chang, Brandon Wadas, Christopher S. Brower, Zhen-Hua Song, Zhi-Liang Xu, Yong-Liang Shang, Wei-Xiao Liu, Li-Na Wang, Wen Dong, Alexander Varshavsky, Rong-Gui Hu, and Wei Li Degradation of the Separase-cleaved Rec8, a Meiotic Cohesin Subunit, by the N-end Rule Pathway J. Biol. Chem. 2016 291: 7426-. doi:10.1074/jbc.M116.714964
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64543
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Feb 2016 18:20
Last Modified:15 Nov 2017 00:15

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