Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice.
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| Abstract |
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.
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| Authors | Young Sun Oh, Dae Gyu Kim, Gyuyoup Kim, Eung-Chil Choi, Brian K Kennedy, Yousin Suh, Bum Joon Park, Sunghoon Kim |
| Journal | Aging cell (Aging Cell) Vol. 9 Issue 5 Pg. 810-22 (Oct 2010) ISSN: 1474-9726 [Electronic] England |
| PMID | 20726853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
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