The ubiquitin ligase Ubr2, a recognition E3 component of the N-end rule pathway, stabilizes Tex19.1 during spermatogenesis

• Published in: PloS one Vol. 5; no. 11; p. e14017
• Main Authors: Yang, Fang, Cheng, Yong, An, Jee Young, Kwon, Yong Tae, Eckardt, Sigrid, Leu, N Adrian, McLaughlin, K John, Wang, Peijing Jeremy
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.11.2010; Public Library of Science (PLoS)
• Subjects: Animals; Binding; Binding Sites - genetics; Biology; Blotting, Western; Cloning; Cysteine; Cysteine - genetics; Defects; Deficient mutant; Deoxyribonucleic acid; Developmental Biology/Germ Cells; DNA; Embryos; Experiments; Female; Females; Genes; Genetics and Genomics/Animal Genetics; Germ cells; Immunoglobulins; Immunoprecipitation; Laboratories; Lethality; Ligases; Male; Mammals; Mass spectrometry; Medical research; Meiosis; Methionine - genetics; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mutation; NIH 3T3 Cells; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pharmaceutical sciences; Proteasomes; Protein Binding; Protein Stability; Proteins; Proteolysis; Recognition; Saccharomyces cerevisiae; Scientific imaging; Signal Transduction; Spermatogenesis; Substrates; Testes; Testis - cytology; Testis - metabolism; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; Urology/Infertility; Veterinary colleges; Veterinary medicine; Ohio; Pittsburgh Pennsylvania; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0014017

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.