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The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis.
- Source :
- PLoS ONE, Vol 6, Iss 10, p e25871 (2011)
- Publication Year :
- 2011
- Publisher :
- Public Library of Science (PLoS), 2011.
-
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.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 6
- Issue :
- 10
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.03f823a97dad474ba8cd3be68901be9c
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0025871