The E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis

by Masashi Kajiro, Mai Tsuchiya, Yoh-ichi Kawabe, Ryohei Furumai, Naoya Iwasaki, Yuki Hayashi, Miyuki Katano, Yuka Nakajima, Natsuka Goto, Tatsuya Watanabe, Akiko Murayama, Hisashi Oishi, Masatsugu Ema, Satoru Takahashi, Hiroyuki Kishimoto, Junn Yanagisawa

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 (Trip12mt/mt) that disrupts the ubiquitin ligase activity resulted in embryonic lethality in the middle stage of development. Trip12mt/mt embryos exhibited growth arrest and increased expression of the negative cell cycle regulator p16 [7], [8], [9], [10]. In contrast, Trip12mt/mt ES cells were viable. They had decreased proliferation, but maintained both the undifferentiated state and the ability to differentiate. Trip12mt/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.

For the full article visit:
The E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis
Syndicated from:PLoS ONE

Article is licensed under a Creative Commons Attribution License.