The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis

Abstract

Protein ubiquitination is a post-translational protein modification that regulates many biological conditions [1, 2, 3, 4]. Trip12 is a HECT-type E3 ubiquitin ligase that ubiquitinates ARF and APP-BP1 [5, 6]. 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 [7, 8, 9, 10]. 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. © 2011 Kajiro et al.