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PMID:14585983
| Citation |
Kwon, YT, Xia, Z, An, JY, Tasaki, T, Davydov, IV, Seo, JW, Sheng, J, Xie, Y and Varshavsky, A (2003) Female lethality and apoptosis of spermatocytes in mice lacking the UBR2 ubiquitin ligase of the N-end rule pathway. Mol. Cell. Biol. 23:8255-71 |
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| Abstract |
Substrates of the ubiquitin-dependent N-end rule pathway include proteins with destabilizing N-terminal residues. UBR1(-/-) mice, which lacked the pathway's ubiquitin ligase E3alpha, were viable and retained the N-end rule pathway. The present work describes the identification and analysis of mouse UBR2, a homolog of UBR1. We demonstrate that the substrate-binding properties of UBR2 are highly similar to those of UBR1, identifying UBR2 as the second E3 of the mammalian N-end rule pathway. UBR2(-/-) mouse strains were constructed, and their viability was found to be dependent on both gender and genetic background. In the strain 129 (inbred) background, the UBR2(-/-) genotype was lethal to most embryos of either gender. In the 129/B6 (mixed) background, most UBR2(-/-) females died as embryos, whereas UBR2(-/-) males were viable but infertile, owing to the postnatal degeneration of the testes. The gross architecture of UBR2(-/-) testes was normal and spermatogonia were intact as well, but UBR2(-/-) spermatocytes were arrested between leptotene/zygotene and pachytene and died through apoptosis. A conspicuous defect of UBR2(-/-) spermatocytes was the absence of intact synaptonemal complexes. We conclude that the UBR2 ubiquitin ligase and, hence, the N-end rule pathway are required for male meiosis and spermatogenesis and for an essential aspect of female embryonic development. |
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| Keywords |
Amino Acid Sequence; Animals; Apoptosis; Base Sequence; Cell Line; Chromosome Pairing; DNA, Complementary/genetics; Embryonic and Fetal Development; Female; Genes, Lethal; Infertility, Male/enzymology; Infertility, Male/genetics; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; NIH 3T3 Cells; Sequence Homology, Amino Acid; Spermatocytes/enzymology; Spermatocytes/pathology; Spermatogenesis; Testis/enzymology; Testis/pathology; Transfection; Ubiquitin-Protein Ligases/deficiency; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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