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

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.

• Authors: S Dominici, V Fiori, M Magnani, E Schena, C Capanni, D Camozzi, M R D'Apice, C Le Dour, M Auclair, M Caron, G Novelli, C Vigouroux, N M Maraldi, G Lattanzi
• Journal: European journal of histochemistry : EJH (Eur J Histochem) 2009 Jan-Mar Vol. 53 Issue 1 Pg. 43-52 ISSN: 1121-760X [Print] Italy
• PMID: 19351612 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lamin Type A
• Membrane Proteins
• Nuclear Proteins
• Protein Precursors
• prelamin A
• Endopeptidases
• prelamin A endoprotease
• Metalloendopeptidases
• ZMPSTE24 protein, human

Topics

• Amino Acid Sequence
• Animals
• Endopeptidases (metabolism)
• Fibroblasts (metabolism)
• Humans
• Lamin Type A
• Membrane Proteins (antagonists & inhibitors, physiology)
• Metalloendopeptidases (antagonists & inhibitors, physiology)
• Nuclear Proteins (metabolism)
• Progeria (metabolism, pathology)
• Protein Precursors (metabolism)
• Protein Prenylation
• Rabbits (immunology)