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Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria
- Source :
- Europe PubMed Central, European Journal of Histochemistry, Vol 53, Iss 1, Pp e6-e6 (2009), European Journal of Histochemistry : EJH, European Journal of Histochemistry, Vol 53, Iss 1, Pp 43-52 (2009), Scopus-Elsevier
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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.
- Subjects :
- congenital, hereditary, and neonatal diseases and abnormalities
Histology
Protein Prenylation
Biophysics
Laminopathy
Progeroid syndromes
HIV-protease inhibitors
Progeria
Endopeptidases
medicine
Animals
Humans
Amino Acid Sequence
Protein Precursors
Nuclear protein
lcsh:QH301-705.5
anti-prelamin A antibodies
FTI-277
Original Paper
prelamin A
integumentary system
Chemistry
laminopathies
Membrane Proteins
Metalloendopeptidases
Nuclear Proteins
nutritional and metabolic diseases
Cell Biology
Fibroblasts
Lamin Type A
medicine.disease
AFCMe
Cell biology
lcsh:Biology (General)
Membrane protein
Protein prenylation
Nuclear lamina
Rabbits
Lamin
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Europe PubMed Central, European Journal of Histochemistry, Vol 53, Iss 1, Pp e6-e6 (2009), European Journal of Histochemistry : EJH, European Journal of Histochemistry, Vol 53, Iss 1, Pp 43-52 (2009), Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....be070e3eba062fc4cbc8c4ff5b77da94