We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The mouse polyubiquitin gene UbC is essential for fetal liver development, cell-cycle progression and stress tolerance.
- Authors
Kwon-Yul Ryu; Maehr, René; Gilchrist, Catherine A.; Long, Michael A.; Bouley, Donna M.; Mueller, Britta; Ploegh, Hidde L.; Kopito, Ron R.
- Abstract
UbC is one of two stress-inducible polyubiquitin genes in mammals and is thought to supplement the constitutive UbA genes in maintaining cellular ubiquitin (Ub) levels during episodes of cellular stress. We have generated mice harboring a targeted disruption of the UbC gene. UbC−/− embryos die between embryonic days 12.5 and 14.5 in utero, most likely owing to a severe defect in liver cell proliferation. Mouse embryonic fibroblasts from UbC−/− embryos exhibit reduced growth rates, premature senescence, increased apoptosis and delayed cell-cycle progression, with slightly, but significantly, decreased steady-state Ub levels. UbC−/− fibroblasts are hypersensitive to proteasome inhibitors and heat shock, and unable to adequately increase Ub levels in response to these cellular stresses. Most, but not all of the UbC−/− phenotypes can be rescued by providing additional Ub from a poly hemagglutinin-tagged Ub minigene expressed from the Hprt locus. We propose that UbC is regulated by a process that senses Ub pool dynamics. These data establish that UbC constitutes an essential source of Ub during cell proliferation and stress that cannot be compensated by other Ub genes.
- Publication
EMBO Journal, 2007, Vol 26, Issue 11, p2693
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1038/sj.emboj.7601722