The E3 ubiquitin ligase activity of Trip12 is essential for mouse embryogenesis.
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.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
Masashi
M
Kajiro
Mai
M
Tsuchiya
Yoh-Ichi
Y
Kawabe
Ryohei
R
Furumai
Naoya
N
Iwasaki
Yuki
Y
Hayashi
Miyuki
M
Katano
Yuka
Y
Nakajima
Natsuka
N
Goto
Tatsuya
T
Watanabe
Akiko
A
Murayama
Hisashi
H
Oishi
Masatsugu
M
Ema
Satoru
S
Takahashi
Hiroyuki
H
Kishimoto
Junn
J
Yanagisawa
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D009154:Mutation; D010641:Phenotype; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D059467:Transcriptome; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D019941:Cyclin-Dependent Kinase Inhibitor p16; C465207:Smarce1 protein, mouse; C570199:Trip12 protein, mouse; D044767:Ubiquitin-Protein Ligases