Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria
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 yie...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2009-08-01
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| Series: | European Journal of Histochemistry |
| Online Access: | http://www.ejh.it/index.php/ejh/article/view/1232 |
| _version_ | 1818808331286872064 |
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| author | S Dominici 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 |
| author_facet | S Dominici 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 |
| author_sort | S Dominici |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T19:39:51Z |
| format | Article |
| id | doaj.art-ad6c0bc5b2b14daa90145320f0c29602 |
| institution | Directory Open Access Journal |
| issn | 1121-760X 2038-8306 |
| language | English |
| last_indexed | 2024-12-18T19:39:51Z |
| publishDate | 2009-08-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | European Journal of Histochemistry |
| spelling | doaj.art-ad6c0bc5b2b14daa90145320f0c296022022-12-21T20:55:29ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062009-08-01531e6e610.4081/ejh.2009.e6849Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeriaS DominiciV FioriM MagnaniE SchenaC CapanniD CamozziMR D’ApiceC Le DourM AuclairM CaronG NovelliC VigourouxNM MaraldiG LattanziLamin 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.http://www.ejh.it/index.php/ejh/article/view/1232 |
| spellingShingle | S Dominici 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 Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria European Journal of Histochemistry |
| title | Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria |
| title_full | Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria |
| title_fullStr | Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria |
| title_full_unstemmed | Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria |
| title_short | Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria |
| title_sort | different prelamin a forms accumulate in human fibroblasts a study in experimental models and progeria |
| url | http://www.ejh.it/index.php/ejh/article/view/1232 |
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