| First Author | Oh YS | Year | 2010 |
| Journal | Aging Cell | Volume | 9 |
| Issue | 5 | Pages | 810-22 |
| PubMed ID | 20726853 | Mgi Jnum | J:217053 |
| Mgi Id | MGI:5612959 | Doi | 10.1111/j.1474-9726.2010.00614.x |
| Citation | Oh YS, et al. (2010) Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice. Aging Cell 9(5):810-22 |
| abstractText | 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. |
