Association of progerin-interactive partner proteins with lamina proteins: Mel18 is associated with emerin in HGPS

Beijing Da Xue Xue Bao Yi Xue Ban. 2009 Aug 18;41(4):397-401.

Abstract

Objective: The Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a childhood disorder with features of premature aging and is caused by mutations in the lamin A gene resulting in the production of an abnormal protein, termed progerin. To investigate the underlying pathogenic mechanism, we studied the nuclear co-localization and association of progerin interactive partner proteins (PIPPs) with lamina proteins.

Methods: Both wild-type (WT) and progeria fibroblasts were studied by various methods including confocal microscopy, immunoprecipitation and Western blot.

Results: All PIPPs discovered so-far co-localized with lamin A/C. In addition, the PIPPs were selectively associated with lamina proteins. An increased immunofluorescent staining signal was found for Mel18 in HGPS as compared to WT cells. An association of Mel18 with emerin was observed in HGPS, but not in WT cells.

Conclusion: Based on these findings, we propose that PIPPs, along with associated lamina proteins may form a pathogenic progerin-containing protein complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lamin Type A / metabolism*
  • Membrane Proteins / metabolism*
  • Mutation
  • Nuclear Lamina / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polycomb Repressive Complex 1
  • Progeria / metabolism*
  • Progeria / pathology
  • Protein Binding
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Repressor Proteins / metabolism*

Substances

  • Lamin Type A
  • Membrane Proteins
  • Nuclear Proteins
  • PCGF6 protein, human
  • Protein Precursors
  • Repressor Proteins
  • emerin
  • prelamin A
  • Polycomb Repressive Complex 1