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PMID:22028794
Citation |
Kajiro, M, Tsuchiya, M, Kawabe, Y, Furumai, R, Iwasaki, N, Hayashi, Y, Katano, M, Nakajima, Y, Goto, N, Watanabe, T, Murayama, A, Oishi, H, Ema, M, Takahashi, S, Kishimoto, H and Yanagisawa, J (2011) The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis. PLoS ONE 6:e25871 |
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Abstract |
Protein ubiquitination is a post-translational protein modification that regulates many biological conditions. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1. However, the significance of Trip12 in vivo is largely unknown. Here we show that the ubiquitin ligase activity of Trip12 is indispensable for mouse embryogenesis. A homozygous mutation in Trip12 (Trip12(mt/mt)) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12(mt/mt) embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16. In contrast, Trip12(mt/mt) ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12(mt/mt) ES cells had increased levels of the BAF57 protein (a component of the SWI/SNF chromatin remodeling complex) and altered gene expression patterns. These data suggest that Trip12 is involved in global gene expression and plays an important role in mouse development. |
Links |
PubMed PMC3196520 Online version:10.1371/journal.pone.0025871 |
Keywords |
Animals; Cell Cycle/genetics; Chromosomal Proteins, Non-Histone/chemistry; Chromosomal Proteins, Non-Histone/metabolism; Cyclin-Dependent Kinase Inhibitor p16/metabolism; Embryo, Mammalian/metabolism; Embryonic Development/genetics; Embryonic Stem Cells/metabolism; Female; Male; Mice; Mutation; Phenotype; Protein Stability; Protein Structure, Tertiary; Transcriptome; Ubiquitin-Protein Ligases/chemistry; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
GO:0006464: protein modification process |
ECO:0000315: |
P |
Figure 2 |
complete | ||||
involved_in |
GO:0045995: regulation of embryonic development |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0045995: regulation of embryonic development |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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