Degradation of the separase-cleaved REC8, a meiotic cohesin subunit, by the N-end rule pathway




Liu, Yu-Jiao
Chang, ZeNan
Wadas, Brandon
Brower, Christopher S.
Song, Zhen-Hua
Xu, Zhi-Liang
Shang, Yong-Liang
Liu, Wei-Xiao
Wang, Li-Na
Dong, Wen

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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.



Meiosis, Protein degradation, Proteolysis, Spermatogenesis, Ubiquitin


This is the published version of an article that is available at Recommended citation: Liu, Y.-J., Liu, C., Chang, Z. N., Wadas, B., Brower, C. S., Song, Z.-H., Xu, Z.-L., Shang, Y.-L., Liu, W.-X., Wang, L.-N., Dong, W., Varshavsky, A., Hu, R.-G., & Li, W. (2016). Degradation of the separase-cleaved REC8, a meiotic cohesin subunit, by the N-end rule pathway. Journal of Biological Chemistry, 291(14), 7426–7438. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.