title: Degradation of the Separase-cleaved Rec8, a Meiotic Cohesin Subunit, by the N-end Rule Pathway.
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 yeastSaccharomyces 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-confinedAte1(-/-)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 maleAte1(-/-)mice are nearly infertile, due to massive apoptotic death ofAte1(-/-)spermatocytes during the metaphase of meiosis I. These effects ofAte1ablation 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.
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, the College of Marine Life, Ocean University of China, Qingdao 266003, China, and.
authors: Yu-Jiao
authors: YJ
authors: Liu
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, the University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Chao
authors: C
authors: Liu
authors: the Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125.
authors: ZeNan
authors: Z
authors: Chang
authors: the Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125.
authors: Brandon
authors: B
authors: Wadas
authors: the Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, the Department of Biology, Texas Woman's University, Denton, Texas 76204.
authors: Christopher S
authors: CS
authors: Brower
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, the University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Zhen-Hua
authors: ZH
authors: Song
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, the University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Zhi-Liang
authors: ZL
authors: Xu
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, the University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Yong-Liang
authors: YL
authors: Shang
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Wei-Xiao
authors: WX
authors: Liu
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, the University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Li-Na
authors: LN
authors: Wang
authors: the College of Marine Life, Ocean University of China, Qingdao 266003, China, and wdong@ouc.edu.cn.
authors: Wen
authors: W
authors: Dong
authors: the Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, avarsh@caltech.edu.
authors: Alexander
authors: A
authors: Varshavsky
authors: the State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China coryhu@sibs.ac.cn.
authors: Rong-Gui
authors: RG
authors: Hu
authors: From the State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, leways@ioz.ac.cn.
authors: Wei
authors: W
authors: Li
mesh_terms: D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D008297:Male; D008677:Metaphase; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D064247:Separase / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C465862:Rad21 protein, mouse; C465863:Rec8 protein, mouse; D019881:Aminoacyltransferases; C019727:arginyltransferase; D064247:Separase
keywords: meiosis; protein degradation; proteolysis; spermatogenesis; ubiquitin