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Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice.

Authors: Oh, YS  Kim, DG  Kim, G  Choi, EC  Kennedy, BK  Suh, Y  Park, BJ  Kim, S 
Citation: Oh YS, etal., Aging Cell. 2010 Oct;9(5):810-22. doi: 10.1111/j.1474-9726.2010.00614.x.
Pubmed: (View Article at PubMed) PMID:20726853
DOI: Full-text: DOI:10.1111/j.1474-9726.2010.00614.x

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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CRRD Object Information
CRRD ID: 10401221
Created: 2015-10-02
Species: All species
Last Modified: 2015-10-02
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.