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 Citations (Scopus)

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 2010

Fingerprint

Lamin Type A
Down-Regulation
Phenotype
Transgenic Mice
Neoplasms
Progeria
Amino Acyl-tRNA Synthetases
Proteasome Endopeptidase Complex
Protein Isoforms
Proteins
prelamin A

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Aging

Cite this

Oh, Y. S., Kim, D. G., Kim, G., Choi, E. C., Kennedy, B. K., Suh, Y., ... 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

Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice. / Oh, Young Sun; Kim, Dae Gyu; Kim, Gyuyoup; Choi, Eung Chil; Kennedy, Brian K.; Suh, Yousin; Park, Bum Joon; Kim, Sunghoon.

In: Aging Cell, Vol. 9, No. 5, 10.2010, p. 810-822.

Research output: Contribution to journalArticle

Oh, YS, Kim, DG, Kim, G, Choi, EC, Kennedy, BK, Suh, Y, Park, BJ & Kim, S 2010, 'Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice', Aging Cell, vol. 9, no. 5, pp. 810-822. https://doi.org/10.1111/j.1474-9726.2010.00614.x
Oh, Young Sun ; Kim, Dae Gyu ; Kim, Gyuyoup ; Choi, Eung Chil ; Kennedy, Brian K. ; Suh, Yousin ; Park, Bum Joon ; Kim, Sunghoon. / Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice. In: Aging Cell. 2010 ; Vol. 9, No. 5. pp. 810-822.
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