Proliferation of progeria cells is enhanced by lamina-associated polypeptide 2α (LAP2α) through expression of extracellular matrix proteins

Genes Dev. 2015 Oct 1;29(19):2022-36. doi: 10.1101/gad.263939.115.


Lamina-associated polypeptide 2α (LAP2α) localizes throughout the nucleoplasm and interacts with the fraction of lamins A/C that is not associated with the peripheral nuclear lamina. The LAP2α-lamin A/C complex negatively affects cell proliferation. Lamins A/C are encoded by LMNA, a single heterozygous mutation of which causes Hutchinson-Gilford progeria syndrome (HGPS). This mutation generates the lamin A variant progerin, which we show here leads to loss of LAP2α and nucleoplasmic lamins A/C, impaired proliferation, and down-regulation of extracellular matrix components. Surprisingly, contrary to wild-type cells, ectopic expression of LAP2α in cells expressing progerin restores proliferation and extracellular matrix expression but not the levels of nucleoplasmic lamins A/C. We conclude that, in addition to its cell cycle-inhibiting function with lamins A/C, LAP2α can also regulate extracellular matrix components independently of lamins A/C, which may help explain the proliferation-promoting function of LAP2α in cells expressing progerin.

Keywords: A-type lamins; Hutchinson Gilford progeria; cell proliferation regulation; extracellular matrix; lamina-associated polypeptide; nuclear lamina; nucleoplasmic lamins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation / genetics
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation*
  • Extracellular Matrix Proteins / genetics*
  • Humans
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Progeria / genetics
  • Progeria / physiopathology*
  • Up-Regulation


  • DNA-Binding Proteins
  • Extracellular Matrix Proteins
  • LMNA protein, human
  • Lamin Type A
  • Membrane Proteins
  • lamina-associated polypeptide 2
  • prelamin A