title: The ubiquitin ligase Ubr2, a recognition E3 component of the N-end rule pathway, stabilizes Tex19.1 during spermatogenesis.
abstract: Ubiquitin E3 ligases target their substrates for ubiquitination, leading to proteasome-mediated degradation or altered biochemical properties. The ubiquitin ligase Ubr2, a recognition E3 component of the N-end rule proteolytic pathway, recognizes proteins with N-terminal destabilizing residues and plays an important role in spermatogenesis. Tex19.1 (also known as Tex19) has been previously identified as a germ cell-specific protein in mouse testis. Here we report that Tex19.1 forms a stable protein complex with Ubr2 in mouse testes. The binding of Tex19.1 to Ubr2 is independent of the second position cysteine of Tex19.1, a putative target for arginylation by the N-end rule pathway R-transferase. The Tex19.1-null mouse mutant phenocopies the Ubr2-deficient mutant in three aspects: heterogeneity of spermatogenic defects, meiotic chromosomal asynapsis, and embryonic lethality preferentially affecting females. In Ubr2-deficient germ cells, Tex19.1 is transcribed, but Tex19.1 protein is absent. Our results suggest that the binding of Ubr2 to Tex19.1 metabolically stabilizes Tex19.1 during spermatogenesis, revealing a new function for Ubr2 outside the conventional N-end rule pathway.
authors.affiliation: Department of Animal Biology, Center for Animal Transgenesis and Germ Cell Research, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Jee Young
authors.initials: JY
authors.lastname: An
authors.forename: Yong Tae
authors.initials: YT
authors.lastname: Kwon
authors.forename: Sigrid
authors.initials: S
authors.lastname: Eckardt
authors.forename: N Adrian
authors.initials: NA
authors.lastname: Leu
authors.forename: K John
authors.initials: KJ
authors.lastname: McLaughlin
authors.forename: Peijing Jeremy
authors.initials: PJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D003545:Cysteine / Q000235:genetics; D005260:Female; D047468:Immunoprecipitation; D008297:Male; D008715:Methionine / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C528631:Tex19 protein, mouse; D008715:Methionine; C511160:UBR2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D003545:Cysteine