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

Young Sun Oh, Dae Gyu Kim, Gyuyoup Kim, Eung Chil Choi, Brian K. Kennedy, Yousin Suh, Bum Joon Park, Sunghoon Kim

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)810-822
Number of pages13
JournalAging cell
Volume9
Issue number5
DOIs
StatePublished - Oct 1 2010

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Keywords

  • AIMP3/p18
  • Aging
  • LaminA
  • Progeroid
  • Tumor suppressor

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Oh, Y. S., Kim, D. G., Kim, G., Choi, E. C., Kennedy, B. K., Suh, Y., Park, B. J., & Kim, S. (2010). Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice. Aging cell, 9(5), 810-822. https://doi.org/10.1111/j.1474-9726.2010.00614.x