Disease relevance of Nuclear Lamina

• Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina [1].
• By contrast, lamin A and C molecules harboring a point mutation (R482W), which gives rise to a dominant form of familial partial lipodystrophy, behave in a manner that is indistinguishable from wild-type lamins A and C, at least with respect to targeting and assembly within the nuclear lamina [2].
• Lamin B is the major constituent of the nuclear lamina of undifferentiated mouse embryonal carcinoma cells [3].
• Using immunofluorescence on HEp-2 cells, specific enzyme-linked immunosorbent assay, and Western blotting performed against nuclear lamina preparation from Ehrlich ascites tumor cells, we characterized three patients, whose sera contained antibodies to nuclear lamins [4].
• M50/p35 recruits the cellular protein kinase C for phosphorylation and dissolution of the nuclear lamina, suggesting that herpesviruses target a critical element of nuclear architecture [5].

High impact information on Nuclear Lamina

• These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies [6].
• This region contains the lamin A/C gene (LMNA), a candidate gene encoding two proteins of the nuclear lamina, lamins A and C, produced by alternative splicing [7].
• Lamin A is a major component of the nuclear lamina and nuclear skeleton [8].
• The mammalian nuclear lamina protein lamin B1 is posttranslationally modified by farnesylation, endoproteolysis, and carboxymethylation at a carboxyl-terminal CAAX motif [9].
• Nup153 is a peripheral NPC component that has been implicated in protein and RNP transport and in the interaction of NPCs with the nuclear lamina [10].

Biological context of Nuclear Lamina

• Double immunofluorescence experiments performed with anti-NuMA and antilamin antibodies indicate that NuMA dissociates from condensing chromosomes during early prophase, before the complete disintegration of the nuclear lamina [11].
• Deficiency in the endoproteolysis or methylation of lamin B1 results in loss of integrity and deformity of the nuclear lamina [9].
• By contrast, cyclin B1 accumulates in the cytoplasm of interphase cells and only enters the nucleus at the beginning of mitosis, before nuclear lamina breakdown [12].
• Barrier-to-autointegration factor is required to segregate and enclose chromosomes within the nuclear envelope and assemble the nuclear lamina [13].
• Second, chelerythrine specifically inhibits betaII PKC-mediated lamin B phosphorylation and mitotic nuclear lamina disassembly [14].

Anatomical context of Nuclear Lamina

• Upon treatment of nuclear envelopes with Triton X-100, gp 190 remains associated with a protein substructure of the nuclear envelope consisting of pore complexes and nuclear lamina [15].
• The A-type lamins, nuclear intermediate filament proteins encoded by the LMNA gene, are basic components of the nuclear lamina [16].
• The nuclear lamina protein lamin A/C is required for FSHD region chromatin localization to the nuclear envelope, as the association is lost in lamin A/C null fibroblasts [17].
• We show that mutations in unc-83 disrupt nuclear migration in a similar manner in migrating P cells, hyp7 precursors and the intestinal primordium, but have no obvious defects in the association of centrosomes with nuclei or the structure of the nuclear lamina of migrating nuclei [18].
• Moreover, breakdown of all other major components of the nuclear lamina, like the inner nuclear membrane proteins and nuclear pore complexes, seems also to depend on cdk1 [19].

Associations of Nuclear Lamina with chemical compounds

• The nuclear lamina proteins, prelamin A, lamin B, and a 70-kD lamina-associated protein, are posttranslationally modified by a metabolite derived from mevalonate [20].
• After treatment with 4 M urea it remains bound to the nuclear lamina in an active state, but it is irreversibly inactivated in 6 M urea [21].
• The Drosophila nuclear lamina protein YA binds to DNA and histone H2B with four domains [22].
• In MVN-treated cells, the lamin A precursor accumulated most strikingly in the peripheral nuclear lamina where it was assembled, while intranuclear foci were maintained [23].
• In addition, lamin C', a modified form of lamin C, not observed in intact nonmuscle cells previously [Glass et al. (1985) J. Biol. Chem. 260, 1895-1900], exists as a native component of the nuclear lamina in rat skeletal myotubes but not in myoblasts [24].

Gene context of Nuclear Lamina

• Here we describe the derivation of mice carrying an autosomal recessive mutation in the lamin A gene (Lmna) encoding A-type lamins, major components of the nuclear lamina [25].
• Zmpste24 is a metalloproteinase required for the processing of prelamin A to lamin A, a structural component of the nuclear lamina [26].
• In contrast, lamin B1 was absent from cardiomyocyte nuclei, showing that lamin B1 is not essential for localization of emerin to the nuclear lamina [27].
• Our results suggest that interactions with lamin might mediate or stabilize the localization of otefin and YA in the nuclear lamina [28].
• Vertebrate Nup53 interacts with the nuclear lamina and is required for the assembly of a Nup93-containing complex [29].

Analytical, diagnostic and therapeutic context of Nuclear Lamina

• Double immunolabeling techniques revealed that nuclear lamina proteins, lamins A, C and B1, and lamin B receptor were colocalized with the antigen(s) recognized by atypical p-ANCA [30].
• Immunoelectron microscopy localized NUP-1 to the inner face of the nuclear envelope, suggesting that it is a major filamentous component of the trypanosome nuclear lamina [31].
• Concomitant with nuclear pyknosis, there were also changes in the nuclear lamina as well as infringement of the nuclear compartment by CP49, as shown by confocal microscopy [32].
• The DNA of high molecular weight (much longer than 50 kbp) behaved as if tightly bound to the nuclear lamina, as judged by sedimentation in sucrose and metrizamide density gradients, electron microscopy, and retention on glass fiber filters [33].
• Visualization of the nuclear lamina in mouse anterior pituitary cells and immunocytochemical detection of lamin A/C by quick-freeze freeze-substitution electron microscopy [34].

References