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Gene Review

Lmna  -  lamin A/C

Rattus norvegicus

Synonyms: Lmn1, Prelamin-A/C
 
 
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Disease relevance of Lmna

 

High impact information on Lmna

  • Effective peptides included the COOH-terminal sequences of all known p21ras proteins as well as those of lamin A and B [3].
  • A synthetic peptide, comprising the first 32 amino acid residues of lamins A and C, is able to fully compete with the intact molecules for binding to lamin B. Conversely, heterotypic A-C associations and homotypic A-A and C-C interactions appear significantly weaker than A/C-B binding and do not involve the lamin A and C amino-terminal domain [4].
  • In addition to the extensive homology to intermediate filament proteins as reported [McKeon, F., Kirschner, M. & Caput, D. (1986) Nature (London) 319, 463-468], a different 82-amino acid residue stretch at the carboxyl terminus of lamin A has been deduced and verified by amino acid sequencing [5].
  • To circumvent potential problems with such analyses, we used reverse transcription/polymerase chain reaction amplification of lamin A/C transcripts from total cytoplasmic RNA [6].
  • Because previous work has indicated that the 46 kD protein may be proteolytically derived from lamins A/C by cleavage at a tyrosine residue at aa376, we investigated the response of lamin A/C transcripts during this regeneration [6].
 

Biological context of Lmna

  • Lamin A gene expression is specifically suppressed in v-src-transformed cells [7].
  • 3. In the present study we describe a group of 21 ARCMT2 patients from seven unrelated Algerian families with the same R298C mutation in the lamin A/C gene and marked variability of the clinical phenotype [8].
  • Recently, a unique homozygous mutation in LMNA, which encodes lamin A/C, a component of the nuclear envelope, was identified in members of three Algerian families with ARCMT2 linked to chromosome 1q21.2-q21 [8].
  • The enhanced caspase-3 activity induced by calcium was inhibited by protease inhibitors affecting morphological nuclear apoptosis except for those responsible for the degradation of lamin A. These results suggest that CaCl2 could trigger, in normal cells, an apoptotic cascade through the activation of cytosolic caspase-3 activity [9].
  • Coimmunoprecipitation experiments revealed that a fraction of lamin A/C formed a stable, SDS-resistant complex with LAP2alpha in interphase cells and in postmetaphase cell extracts [10].
 

Anatomical context of Lmna

  • Approximately 50 to 60% of the lamin B present in matrix-envelope preparations was found in these insoluble membranes while a smaller amount of lamin A and even less of lamin C resisted complete extraction [11].
  • Furthermore, it was found that F9 stem cells and their differentiated progeny express only lamin B, and Northern blotting analysis indicated that these cells fail to accumulate lamin A and C mRNA [12].
  • Seizures rapidly induced cleavage of constitutively expressed caspase-6, followed by elevated VEIDase activity and the proteolysis of lamin A. Neuronal caspase-6 immunoreactivity was markedly upregulated within cortex and hippocampus in relation to bursts of polyspike paroxysmal discharges [13].
  • With longer time in culture, however, these embryonic motor neurons extended extremely long processes on Lmn-1 and on Lmn-2/4/8, while those on Lmn-11 bore shorter neurites with unusually large, flattened growth cones [14].
  • The results of two-dimensional Southwestern and Western analyses pinpointed to size, charge and epitope homology between the 70 kD rat liver nucleoplasmic protein binding the hormone responsive element and the lamin A constituent of nuclear matrix structure [15].
 

Associations of Lmna with chemical compounds

 

Other interactions of Lmna

  • Numerical, but not significantly different increases were found in total abundance of lamin A (NCBI Accession No. 1346413) in the liver, and of 10-formyltetrahydrofolate dehydrogenase (10-FTHF DH, #1346044) and glutathione-S-transferase (GST; #2393724) in the kidneys of vapor-exposed subjects [17].
  • The 70 kD rat liver nucleoplasmic protein binding hormone responsive element of rat haptoglobin gene shares size, charge and epitopes with lamin A [15].
  • The improved assay has been used to analyze the chromatin structure of the lamin A, albumin and alpha-fetoprotein genes during rat liver development [18].
  • We have identified proteins from adult hepatocyte nuclear extracts that are bound to sequences within 28 bp downstream of the transcription initiation site (62 and 48 kDa proteins) and within 20 bp upstream of the initiation site (54 kDa protein), which may function as transcriptional repressors of the lamin A proximal promoter [19].
 

Analytical, diagnostic and therapeutic context of Lmna

  • Surprisingly, Northern blot analyses after CCl4 administration showed low levels of lamin A/C transcripts (which appeared to be predominantly poly[A]-), and we found a decrease in immunoprecipitable lamins A/C from in vitro translation of poly(A)- selected RNA [6].
  • These assays showed a transient, comparatively minor increase in lamin A/C transcripts 1 day after treatment, but levels rapidly declined from 1 to 3 days and were decreased at 3 to 5 days [6].
  • Human autoantibodies reactive against the tail domain exclusive to lamin A and absent from lamin C have been used for immunofluorescence studies on human fibroblast and epithelial cells [20].

References

  1. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Shackleton, S., Lloyd, D.J., Jackson, S.N., Evans, R., Niermeijer, M.F., Singh, B.M., Schmidt, H., Brabant, G., Kumar, S., Durrington, P.N., Gregory, S., O'Rahilly, S., Trembath, R.C. Nat. Genet. (2000) [Pubmed]
  2. Enzymatic modification of Novikoff hepatoma lamins A and C. Glass, W.F., Briggs, J.A., Meredith, M.J., Briggs, R.C., Hnilica, L.S. J. Biol. Chem. (1985) [Pubmed]
  3. Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Reiss, Y., Goldstein, J.L., Seabra, M.C., Casey, P.J., Brown, M.S. Cell (1990) [Pubmed]
  4. Heterotypic and homotypic associations between the nuclear lamins: site-specificity and control by phosphorylation. Georgatos, S.D., Stournaras, C., Blobel, G. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  5. cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Fisher, D.Z., Chaudhary, N., Blobel, G. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  6. Alterations in nuclear scaffold constituents during carbon tetrachloride-induced liver regeneration. Clawson, G.A., Madsen, K.R., Blankenship, L.J., Hatem, C.L. Hepatology (1991) [Pubmed]
  7. Lamin A gene expression is specifically suppressed in v-src-transformed cells. Ozaki, T., Sakiyama, S. FEBS Lett. (1992) [Pubmed]
  8. Phenotypic variability in autosomal recessive axonal Charcot-Marie-Tooth disease due to the R298C mutation in lamin A/C. Tazir, M., Azzedine, H., Assami, S., Sindou, P., Nouioua, S., Zemmouri, R., Hamadouche, T., Chaouch, M., Feingold, J., Vallat, J.M., Leguern, E., Grid, D. Brain (2004) [Pubmed]
  9. Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. Juin, P., Pelletier, M., Oliver, L., Tremblais, K., Grégoire, M., Meflah, K., Vallette, F.M. J. Biol. Chem. (1998) [Pubmed]
  10. Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. Dechat, T., Korbei, B., Vaughan, O.A., Vlcek, S., Hutchison, C.J., Foisner, R. J. Cell. Sci. (2000) [Pubmed]
  11. Lamin B from rat liver nuclei exists both as a lamina protein and as an intrinsic membrane protein. Lebel, S., Raymond, Y. J. Biol. Chem. (1984) [Pubmed]
  12. Nuclear lamina heterogeneity in mammalian cells. Differential expression of the major lamins and variations in lamin B phosphorylation. Worman, H.J., Lazaridis, I., Georgatos, S.D. J. Biol. Chem. (1988) [Pubmed]
  13. Expression and differential processing of caspases 6 and 7 in relation to specific epileptiform EEG patterns following limbic seizures. Henshall, D.C., Skradski, S.L., Meller, R., Araki, T., Minami, M., Schindler, C.K., Lan, J.Q., Bonislawski, D.P., Simon, R.P. Neurobiol. Dis. (2002) [Pubmed]
  14. Motor neurons and Schwann cells distinguish between synaptic and extrasynaptic isoforms of laminin. Cho, S.I., Ko, J., Patton, B.L., Sanes, J.R., Chiu, A.Y. J. Neurobiol. (1998) [Pubmed]
  15. The 70 kD rat liver nucleoplasmic protein binding hormone responsive element of rat haptoglobin gene shares size, charge and epitopes with lamin A. Sevaljević, L., Sekularac, S. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  16. Independent expression and assembly properties of heterologous lamins A and C in murine embryonal carcinomas. Horton, H., McMorrow, I., Burke, B. Eur. J. Cell Biol. (1992) [Pubmed]
  17. Toxicity of chemical mixtures: proteomic analysis of persisting liver and kidney protein alterations induced by repeated exposure of rats to JP-8 jet fuel vapor. Witzmann, F.A., Carpenter, R.L., Ritchie, G.D., Wilson, C.L., Nordholm, A.F., Rossi, J. Electrophoresis (2000) [Pubmed]
  18. An improved method to distinguish micrococcal nuclease sensitivity of chromatin. Hamid, Q.A., Thanumalayan, S., Parnaik, V.K. J. Biochem. Biophys. Methods (1996) [Pubmed]
  19. Identification of altered DNA-protein interactions at the lamin A proximal promoter in quiescent hepatocytes. Tiwari, B., Parnaik, V.K. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  20. Differential accessibility of the tail domain of nuclear lamin A in interphase and mitotic cells. Collard, J.F., Senécal, J.L., Raymond, Y. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
 
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