Disease relevance of Lmnb1

• Because of this key importance of lamin B, cDNA clones encoding mammalian lamin B were isolated by screening murine cDNA libraries, representing F9 teratocarcinoma cells and fetal liver, with the corresponding cDNA probe of lamin LI of Xenopus laevis [1].
• Embryonal carcinoma (EC) cells express lamin B but not lamin A/C [2].
• Immunoblotting of GCDC-treated McNtcp.24 hepatoma cells demonstrated cleavage of poly(ADP-ribose) polymerase and lamin B1 to fragments that indicate activation of effector caspases [3].
• In vitro phosphorylation of lamin B by protein kinase C in friend erythroleukemia. Effect of chemically induced differentiation [4].

High impact information on Lmnb1

• Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B [5].
• Embryos up to day 8 of gestation and embryonal carcinoma (EC) cells express only a single lamin species closely resembling, if not identical to, lamin B. Lamins A and/or C were detected in fertilized eggs, but disappear during the first 2-4 cleavage divisions, only reappearing in 8 day post-implantation embryos [5].
• During the anaphase-telophase transition, lamin B1 begins to become concentrated at the surface of the chromosomes [6].
• Furthermore, the nuclear staining patterns seen with antibodies directed against lamins A and C in mid-late S-phase do not coalign with the lamin B/BrDU-containing structures [7].
• In this report we demonstrate that during mid-late S-phase, nuclear foci detected with lamin B antibodies are coincident with sites of DNA replication as detected by the colocalization of sites of incorporation of bromodeoxyuridine (BrDU) or proliferating cell nuclear antigen (PCNA) [7].

Biological context of Lmnb1

• Homozygous Lmnb1 mutant mice survived embryonic development but died at birth with defects in lung and bone [8].
• The mutation resulted in the synthesis of a mutant lamin B1 protein lacking several key functional domains, including a portion of the rod domain, the nuclear localization signal, and the CAAX motif (the carboxyl-terminal signal for farnesylation) [8].
• Structural analyses revealed that the lamin B1 gene spans about 43 kb of the genome and consists of 11 exons and 10 introns [9].
• The presumptive promoter region has high GC content and contains a CAAT box and multiple SP1 sites but no classical TATA box, suggesting that the lamin B1 gene has a typical housekeeping gene promoter with a CpG island [9].
• In contrast to anti-lamin B, anti-lamin AC does not bind to the germ cells at any stage of spermatogenesis [10].

Anatomical context of Lmnb1

• Its position on two-dimensional gel suggested that p70 is nuclear envelope lamin B. This possibility was confirmed by the co-migration of p70 with the lamin fraction of mouse liver and its immunoprecipitation with antinuclear lamina antibody [11].
• Lamin B also conforms to the general molecular organization principle of the members of the intermediate filament (IF) protein family, i.e., an extended alpha-helical rod domain that is interrupted by two non alpha-helical linkers and flanked by non-alpha-helical head (amino-terminal) and tail (carboxy-terminal) domains [1].
• On immunoblots anti-lamin B reacts with a approximately 68 kD polypeptide in all germ cells and, to a lesser extent, with four additional polypeptides present only in meiotic and post-meiotic nuclear matrices [10].
• Anti-lamin B binds to the nuclear periphery of all cell types examined, including Sertoli cells, primitive type A spermatogonia, preleptotene, leptotene, zygotene and pachytene spermatocytes, and round spermatids [10].
• In mouse morulae or blastocysts, lamins A/C are no longer recognized, although lamin B remains [12].

Associations of Lmnb1 with chemical compounds

• Evidence for modification of lamin B by a product of mevalonic acid [13].
• The composition and organization of the nuclear lamina of mammalian spermatogenic cells differ significantly from that of somatic cells as they express lamin B1 as well as two short germ line-specific isoforms, namely lamins B3 and C2 [14].
• Farnesyl-pyrophosphate is required for the posttranslational modification of G proteins including p21 ras, prelamin A and lamin B, each of which plays an essential role in cell proliferation [15].

Regulatory relationships of Lmnb1

• Lamin B2 is coexpressed with lamin B1 (formerly termed lamin B) in all somatic cells and mammalian species that we analysed, including a variety of cells currently believed to contain only a single lamin [16].
• The occurrence of nuclear abnormalities was reduced when lamin B1 was coexpressed with mutant lamin A, emphasizing the functional interaction of the two types of lamins [17].
• The cleavage of lamin B was inhibited by caspase inhibitors [18].

Other interactions of Lmnb1

• This view and earlier results on lamin B predict multiple post-translational modifications shared by lamins A and B. While retained by lamin B, which is present in all cells, they are lost by maturation from lamin A, which probably acts only as an additional lamina constituent in differentiated cells [19].
• Apoptosis was accompanied by the processing and activation of CPP32 and Mch3 alpha, together with the cleavage of poly(ADP-ribose) polymerase and lamin B1 [20].
• The results agree in that a major part of the enzyme co-localizes with lamin B under physiological conditions, where PARP-1 only has basal activity [21].
• Apoptosis induced by IL-3 deprivation but not BSO also caused lamin B1 cleavage, suggesting activation of caspase-6 [22].
• In eggs collected at the pronuclear stage and cultured to the late two-cell stage in the presence of alpha-amanitin, the matrix morphology was altered for Pl1 and Pl2. alpha-Amanitin had no affect on the distribution of P1 or lamin B antigens [23].

Analytical, diagnostic and therapeutic context of Lmnb1

• Western blot analysis of the expression of lamins with specific antibodies indicates that lamin B is expressed throughout liver development, unlike lamins A and C which are absent in fetal liver [24].
• Co-localization of PARP-1 and lamin B in the nuclear architecture: a halo-fluorescence- and confocal-microscopy study [21].

References