An Alternative Splicing Product of the Lamin A/C Gene Lacks Exon 10

Machiels, Barbie M.; Zorenc, Antoine H. G.; Endert, J.; Kuijpers, Helma J.H.; Eys, Guillaume J.J.M. van; Ramaekers, Frans C.S.; Broers, Jos L. V.

doi:10.1074/jbc.271.16.9249

Cited by 170 publications

(109 citation statements)

References 32 publications

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“…The lamin A gene has been mapped to 1q12.1-q23, a region of chromosome 1 that is commonly rearranged in tumours (Kamat et al, 1993). Gene deletion (Kamat et al, 1993) as well as transcriptional and post-transcriptional mechanisms (Lebel et al, 1987;Machiels et al, 1996) have all been implicated in the loss of lamin A or C expression. Therefore an important question is whether changes in lamin expression reflect de-differentiation within the tumour or is a requisite of tumour progression.…”

Section: Discussionmentioning

confidence: 99%

Expression of individual lamins in basal cell carcinomas of the skin

et al. 2001

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In this study we used a unique collection of type specific anti-lamin antibodies to study lamin expression patterns in normal human skin and in skin derived from patients with basal cell carcinomas (BCCs). Lamin expression in serial sections from frozen tissue samples was investigated by single and double indirect immunofluorescence. In normal skin, lamin A was expressed in dermal fibroblasts and in suprabasal epithelial cells but was absent from all basal epithelial cells. Lamin C was expressed in dermal fibroblasts, suprabasal epithelial cells and a majority of basal epithelial cells. However, lamin C was not expressed in quiescent basal epithelial cells. Lamin B 1 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B 2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts. Finally, lamin B 2 was expressed in all cell types in normal skin. Lamin expression was also investigated in a collection of 16 BCCs taken from a variety of body sites. Based upon patterns of lamin expression the BCCs were classified into four groups: A-negative (10/16 tumours), C-negative (5/16 tumours), A/C-negative (1/16 tumours) and A/B 2 -negative (1/16 tumours). Lamin expression was also compared to cell proliferation index by staining serial sections with the proliferation marker Ki67. 9/10 of the lamin A negative tumours were highly proliferative, whereas 4/5 of the lamin C negative tumours were slow growing. Thus as a general rule absence of lamin A was correlated with rapid growth within the tumour, while absence of lamin C was correlated with slow growth within the tumour. Our data supports the hypothesis that lamin A has a negative influence on cell proliferation and its down regulation may be a requisite of tumour progression. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Expression of individual lamins in basal cell carcinomas of the skin

et al. 2001

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“…The LMNA gene encodes three major proteins, lamins A, C1, and C2. Lamin AD10 is not included in the database as it has only been detected in human cell lines and not, so far, in normal tissues [Machiels et al, 1996]. At the time of writing there are altogether 1,235 sequence variants and 168 allelic variants in the database.…”

Section: Database Content and Organizationmentioning

confidence: 99%

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

et al. 2008

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Communicated by A. Jamie CuticchiaWe describe a revised and expanded database on human intermediate filament proteins, a major component of the eukaryotic cytoskeleton. The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. To date, the database catalogs 1,274 manually-curated pathogenic sequence variants and 170 allelic variants in intermediate filament genes from over 459 peer-reviewed research articles. Unrelated cases were collected from all of the six sequence homology groups and the sequence variations were described at cDNA and protein levels with links to the related diseases and reference articles. The mutations and polymorphisms are presented in parallel with data on protein structure, gene, and chromosomal location and basic information on associated diseases. Detailed statistics relating to the variants records in the database are displayed by homology group, mutation type, affected domain, associated diseases, and nucleic and amino acid substitutions. Multiple sequence alignment algorithms can be run from queries to determine DNA or protein sequence conservation. Literature sources can be interrogated within the database and external links are provided to public databases. The database is freely and publicly accessible online at www.interfil.org (last accessed 13 September 2007). Users can query the database by various keywords and the search results can be downloaded. It is anticipated that the Human Intermediate Filament Database (HIFD) will provide a useful resource to study human genome variations for basic scientists, clinicians, and students alike. Hum Mutat 29(3), [351][352][353][354][355][356][357][358][359][360] 2008.

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“…Lamin AD10 has been detected in the normal colon and a variety of carcinoma cell lines. 8 Lamin C2 has an alternative exon 1 compared with lamin C, and is present in germ cells. 9 In contrast to lamins C and C2, the lamins A and AD10 proteins contain CAAX boxes at their C-terminal ends, which undergo farnesylation and other post-translational modifications to become mature proteins.…”

Section: Introductionmentioning

confidence: 99%

Increased expression of the Hutchinson–Gilford progeria syndrome truncated lamin A transcript during cell aging

et al. 2009

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Most cases of the segmental progeroid syndrome, Hutchinson -Gilford progeria syndrome (HGPS), are caused by a de novo dominant mutation within a single codon of the LMNA gene. This mutation leads to the increased usage of an internal splice site that generates an alternative lamin A transcript with an internal deletion of 150 nucleotides, called lamin AD150. The LMNA gene encodes two major proteins of the inner nuclear lamina, lamins A and C, but not much is known about their expression levels. Determination of the overall expression levels of the LMNA gene transcripts is an important step to further the understanding of the HGPS. In this study, we have performed absolute quantification of the lamins A, C and AD150 transcripts in primary dermal fibroblasts from HGPS patients and unaffected age-matched and parent controls. We show that the lamin AD150 transcript is present in unaffected controls but its expression is 4160-fold lower than that in samples from HGPS patients. Analysis of transcript expression during in vitro aging shows that although the levels of lamin A and lamin C transcripts remain unchanged, the lamin AD150 transcript increases in late passage cells from HGPS patients and parental controls. This study provides a new method for LMNA transcript analysis and insights into the expression of the LMNA gene in HGPS and normal cells.

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An Alternative Splicing Product of the Lamin A/C Gene Lacks Exon 10

Cited by 170 publications

References 32 publications

Expression of individual lamins in basal cell carcinomas of the skin

Expression of individual lamins in basal cell carcinomas of the skin

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

Increased expression of the Hutchinson–Gilford progeria syndrome truncated lamin A transcript during cell aging

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