Open AccessDownregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice
Author(s) -
Oh Young Sun,
Kim Dae Gyu,
Kim Gyuyoup,
Choi EungChil,
Kennedy Brian K.,
Suh Yousin,
Park Bum Joon,
Kim Sunghoon
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00614.x
Subject(s) - lamin , progeria , biology , phenotype , transgene , genetically modified mouse , microbiology and biotechnology , downregulation and upregulation , premature aging , nuclear lamina , senescence , cancer research , genetics , nuclear protein , transcription factor , gene , nucleus
Summary Although AIMP3/p18 is normally associated with the macromolecular tRNA synthetase complex, recent reports have revealed a new role of AIMP3 in tumor suppression. In this study, we generated a transgenic mouse that overexpresses AIMP3 and characterized the associated phenotype in vivo and in vitro . Surprisingly, the AIMP3 transgenic mouse exhibited a progeroid phenotype, and the cells that overexpressed AIMP3 showed accelerated senescence and defects in nuclear morphology. We found that overexpression of AIMP3 resulted in proteasome‐dependent degradation of mature lamin A, but not of lamin C, prelamin A, or progerin. The resulting imbalance in the protein levels of lamin A isoforms, namely altered stoichiometry of prelamin A and progerin to lamin A, appeared to be responsible for a phenotype that resembled progeria. An increase in the level of endogenous AIMP3 has been observed in aged human tissues and cells. The findings in this report suggest that AIMP3 is a specific regulator of mature lamin A and imply that enhanced expression of AIMP3 might be a factor driving cellular and/or organismal aging.