Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging

Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4955-60. doi: 10.1073/pnas.0700854104. Epub 2007 Mar 14.


Mutations in the gene encoding nuclear lamin A (LA) cause the premature aging disease Hutchinson-Gilford Progeria Syndrome. The most common of these mutations results in the expression of a mutant LA, with a 50-aa deletion within its C terminus. In this study, we demonstrate that this deletion leads to a stable farnesylation and carboxymethylation of the mutant LA (LADelta50/progerin). These modifications cause an abnormal association of LADelta50/progerin with membranes during mitosis, which delays the onset and progression of cytokinesis. Furthermore, we demonstrate that the targeting of nuclear envelope/lamina components into daughter cell nuclei in early G(1) is impaired in cells expressing LADelta50/progerin. The mutant LA also appears to be responsible for defects in the retinoblastoma protein-mediated transition into S-phase, most likely by inhibiting the hyperphosphorylation of retinoblastoma protein by cyclin D1/cdk4. These results provide insights into the mechanisms responsible for premature aging and also shed light on the role of lamins in the normal process of human aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • G1 Phase
  • HeLa Cells
  • Humans
  • Lamin Type A / metabolism*
  • Lamin Type B / metabolism
  • Methylation
  • Mitosis*
  • Mutant Proteins / metabolism*
  • Nuclear Lamina / metabolism
  • Progeria / pathology
  • Protein Prenylation
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism


  • Lamin Type A
  • Lamin Type B
  • Mutant Proteins
  • Recombinant Fusion Proteins