In vitro posttranslational modification of lamin B cloned from a human T-cell line.

Abstract

Autoimmune diseases are characterized by spontaneously occurring autoantibodies which have proven to be useful reagents for the characterization of specific nuclear proteins. Using a monoclonal autoantibody (72B9) derived from a murine lupus strain, we have cloned a cDNA from the human T-cell line Many eucaryotic cells contain a cytoskeleton composed of 10-to 15-nm filaments and a karyoskeleton (nuclear envelope) made up of a meshlike lattice of 10-nm filaments. These structures, particularly the cytoplasmic filaments, are classically known as intermediate filaments (IF). IF proteins comprise a multigene family which may number 30 or more proteins in a mammalian species (for reviews, see references 3 and 61). This heterogeneous family comprises, at present, five principal types, of which the first four are tissue-specific cytoplasmic filaments. Type V IF proteins are the nuclear lamins, which have only recently been recognized as a distinct class of intermediate filament proteins (for reviews, see references 14 and 16).The lamins form a meshwork of filaments on the inner, or nucleoplasmic, surface of the nuclear envelope. but are no more closely related to each other than to lamin A and appear to be distinct lamins. LMDO, a lamin cloned and sequenced from Drosophila melanogaster (19), is larger than X. laevis L, but smaller than human and amphibian lamin A, and its sequence is sufficiently divergent to suggest that it is also a distinct lamin. Recently the X. laevis LI sequence was used to isolate a mouse lamin clone (FML11-1) whose protein sequence bears striking homology to the amphibian lamin LI (24). Although it lacks immunological identification, the acidic nature and distinct sequence of this lamin clearly distinguish it from mammalian lamins A and C and suggest that it is lamin B (24). Two acidic avian lamin proteins, B, and B2, have been described whose deduced amino acid sequences suggest that they represent structurally distinct B-type lamins (50, 68). However, whereas B1 appears immunologically related to mammalian lamin B, B2 is immunologically related to lamin A (37,64). It therefore appears that most nuclear lamins fall into two dominant but related types, A and B, which are themselves composed of subtypes.Although IF proteins form an insoluble skeleton within the cell, their functional significance is unclear. It is thought that they play some part in cellular differentiation (reviewed in reference 15). However, cell growth and division can proceed in the absence of most IF proteins, suggesting that their presence is not essential (23). The one exception to this appears to be lamin B, which is found in all somatic cells, even those lacking lamins A and C (20, 35, 62) and other IF proteins (48,49). This, together with the fact that the lamins appear to have arisen very early in eucaryote cell evolution (61), has led to the suggestion that the nuclear lamins, and particularly lamin B, may be the ancestors of the cytoplasmic IF proteins (14,61,69). At the least, it is apparent that the cytoplasmic ...

Lamins at a glance

“…A-type lamins are absent in early embryonic cells, but are present in nearly all differentiated cells (Machiels et al, 1996;Röber et al, 1989). B-type lamins are encoded by the LMNB1 (lamin B1) and LMNB2 (lamin B2 and lamin B3) genes, with at least one B-type lamin expressed in all somatic cells (Biamonti et al, 1992;Furukawa and Hotta, 1993;Pollard et al, 1990).…”

The role ofDrosophilaLamin C in muscle function and gene expression

“…A-type lamins are expressed in nearly all differentiated somatic cells and are not essential for cell viability (Fisher et al, 1986). By contrast, B-type lamins are ubiquitously expressed and are essential for cell viability (Biamonti et al, 1992;Harborth et al, 2001;Pollard et al, 1990). Mutations in LMNA, the gene encoding A-type lamins in humans, give rise to at least 12 disorders termed laminopathies, including autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) (Bonne et al, 1999).…”

Up-regulation of Lamin A/C Expression in Epstein-Barr Virus Immortalized B Cells and Burkitt Lymphoma Cell Lines of Activated B Cell Phenotype

“…Accordingly, B lymphoid cells (centrocytes and centroblasts) expressed lamin B1, whereas mantle zone lymphocytes were lamin B1 and B2 positive [14]. Cell lines derived from human neoplasms usually mirrored the lamin expression profile of the cell type they derived from [45][46][47][48].…”