Open AccessThe E3 Ubiquitin Ligase Activity of Trip12 Is Essential for Mouse Embryogenesis
Author(s) -
Masashi Kajiro,
Mai Tsuchiya,
Yoh-ichi Kawabe,
Ryohei Furumai,
Naoya Iwasaki,
Yoshihiko Hayashi,
Miyuki Katano,
Yuka Nakajima,
Nobuharu Gotô,
Tatsuya Watanabe,
Akiko Murayama,
Hisashi Oishi,
Masatsugu Ema,
Satoru Takahashi,
Hiroyuki Kishimoto,
Junn Yanagisawa
Publication year - 2011
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0025871
Subject(s) - ubiquitin ligase , ubiquitin , biology , microbiology and biotechnology , dna ligase , ubiquitin protein ligases , chromatin remodeling , chromatin , genetics , gene
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.