Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria

  • S Dominici | support@pagepress.org
  • V Fiori
  • M Magnani
  • E Schena
  • C Capanni
  • D Camozzi
  • MR D’Apice
  • C Le Dour
  • M Auclair
  • M Caron
  • G Novelli
  • C Vigouroux
  • NM Maraldi
  • G Lattanzi

Abstract

Lamin A is a component of the nuclear lamina mutated in a group of human inherited disorders known as laminopathies. Among laminopathies, progeroid syndromes and lipodystrophies feature accumulation of prelamin A, the precursor protein which, in normal cells, undergoes a multi-step processing to yield mature lamin A. It is of utmost importance to characterize the prelamin A form accumulated in each laminopathy, since existing evidence shows that drugs acting on protein processing can improve some pathological aspects.We report that two antibodies raised against differently modified prelamin A peptides show a clear specificity to full-length prelamin A or carboxymethylated farnesylated prelamin A, respectively. Using these antibodies, we demonstrated that inhibition of the prelamin A endoprotease ZMPSTE24 mostly elicits accumulation of full-length prelamin A in its farnesylated form, while loss of the prelamin A cleavage site causes accumulation of carboxymethylated prelamin A in progeria cells. These results suggest a major role of ZMPSTE24 in the first prelamin A cleavage step.

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Published
2009-08-17
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How to Cite
Dominici, S., Fiori, V., Magnani, M., Schena, E., Capanni, C., Camozzi, D., D’ApiceM., Le Dour, C., Auclair, M., Caron, M., Novelli, G., Vigouroux, C., Maraldi, N., & Lattanzi, G. (2009). Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria. European Journal of Histochemistry, 53(1), e6. https://doi.org/10.4081/ejh.2009.e6