Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors

Stephen A. Adam, Veronika Butin-Israeli, Megan M. Cleland, Takeshi Shimi, Robert D. Goldman

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Lamin A and the B-type lamins, lamin B1 and lamin B2, are translated as pre-proteins that are modified at a carboxyl terminal cAAX motif by farnesylation, proteolysis and carboxymethylation. Lamin A is further processed by proteolysis to remove the farnesyl, but B-type lamins remain permanently farnesylated. Two childhood diseases, hutchinson Gilford progeria syndrome and restrictive dermopathy are caused by defects in the processing of lamin A, resulting in permanent farnesylation of the protein. Farnesyltransferase inhibitors, originally developed to target oncogenic Ras, have recently been used in clinical trials to treat children with hutchinson Gilford progeria syndrome. Lamin B1 and lamin B2 play important roles in cell proliferation and organ development, but little is known about the role of farnesylation in their functions. Treating normal human fibroblasts with farnesyltransferase inhibitors causes the accumulation of unprocessed lamin B2 and lamin A and a decrease in mature lamin B1. Normally, lamins are concentrated at the nuclear envelope or lamina, but when farnesylation is inhibited, the peripheral localization of lamin B2 decreases as its nucleoplasmic levels increase. Unprocessed prelamin A distributes into both the nuclear envelope/lamina and nucleoplasm. Farnesyltransferase inhibitors also cause a rapid cell cycle arrest leading to cellular senescence. This study suggests that the long-term inhibition of protein farnesylation could have unforeseen consequences on nuclear functions.

Original languageEnglish (US)
Pages (from-to)142-150
Number of pages9
JournalNucleus (United States)
Issue number2
StatePublished - Mar 2013


  • Farnesylation
  • Farnesyltransferase inhibitors
  • Lamins
  • Senescence

ASJC Scopus subject areas

  • Cell Biology


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