Disease relevance of LMNB2

• Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy [1].
• Autoantibodies to human nuclear lamin B2 protein. Epitope specificity in different autoimmune diseases [2].

High impact information on LMNB2

• The initiation sites of bidirectional synthesis at the DNA replication origin located at the 3' end of the human lamin B2 gene were investigated [3].
• Few genes have generated as much recent interest as LMNA, LMNB1 and LMNB2, which encode the components of the nuclear lamina [4].
• The proteins bound in vivo at the human lamin B2 DNA replication origin and their precise sites of binding were investigated along the cell cycle utilizing two novel procedures based on immunoprecipitation following UV irradiation with a pulsed laser light source [5].
• Sequences derived from the human lamin B2 origin can serve as a potent activator for the Mcm helicase, and substitution of its thymine clusters with guanine leads to loss of this activation [6].
• We followed the variations of protein-DNA interactions occurring in vivo over the early firing replication origin located near the human lamin B2 gene, in IMR-90 cells synchronized in different moments of the cell cycle [7].

Biological context of LMNB2

• Here we report a thorough characterization of the DNA sequence requirements of the origin associated with the human lamin B2 gene [8].
• Noncanonical DNA elements in the lamin B2 origin of DNA replication [9].
• In vitro protein-DNA interactions at the human lamin B2 replication origin [10].
• The level of lamin B2 phosphorylation was determined after immunoisolation from [32P]orthophosphate labelled cells [11].
• The expression of A-type (lamin A and C) were shown to be downregulated during hibernation, while lamin B2 remained present in hibernating cardiomyocytes in a way similar to embryonic muscle cells [12].

Anatomical context of LMNB2

• Finally, lamin B2 was expressed in all epithelial cells but was not expressed in dermal fibroblasts [13].
• The lamin B2 antibodies appeared to decorate the nuclear lamina in all tissues examined, except hepatocytes, in which very little lamin B2 expression was observed [14].
• In Orc2(delta/-) cells, the association of HsOrc-2 with the lamin B2, beta-globin, and c-myc origins was decreased by 2.8-, 4.9-, and 2.8-fold, respectively, relative to wild-type HCT116 cells [15].
• Lamin B2 modification in synchronously dividing populations of human diploid fibroblasts was determined by 2-dimensional gel electrophoresis and [32P]orthophosphate labelling [11].
• Our observation that lamin B2 expression in the follicle centre cells of the reactive lymph node is low or absent indicates that this lamin subtype is not always expressed in nucleated cells, which is in clear contrast to the results obtained in previous studies in other diseases and in normal tissues [16].

Associations of LMNB2 with chemical compounds

• Since all of the phosphate incorporated into S-phase and G0 lamin B2 was recovered in serine residues we conclude that the S-phase specific phosphopeptide did not represent either of the cdc2 sites associated with entry nuclear lamina breakdown [11].
• Remarkably, no MV is incorporated into lamin B2 translated from a mutant cDNA encoding alanine instead of cysteine in the C-terminal CXXM motif [17].
• The extent of methylation in nascent and genomic DNAs at specific sites was determined as well by bisulfite mapping of CpG sites at the lamin B2, c-myc, and beta-globin origins of replication [18].
• The combination of bromodeoxyuridine labelling, immunopurification of newly synthesized labelled DNA, measurement of the relative abundance of markers in this DNA by quantitative competitive PCR, has allowed the identification within 450 bp of the start-site of DNA replication located at the human lamin B2 gene [19].
• DNA replication initiates in this cell-free system site-specifically at the lamin B2 DNA replication origin, which is also activated in vivo upon release of mimosine-arrested late G1 phase cells into early S phase [20].

Other interactions of LMNB2

• The DNA-binding activity of HsORC1-5, using lamin B2 DNA as substrate, is stimulated by ATP 3- to 5-fold [21].
• Because the chosen fragment does not contain potential GGC forming sequences, these experiments confirm that the lamin B2 origin adopts a structure partly composed of intramolecular TAT triads [9].
• S-phase phosphorylation of lamin B2 [11].
• The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q [22].
• They consisted of a protein exhibiting a novel amino acid sequence; of nuclear lamin B2, RbAp46, and RbAp48; and of four as yet unknown proteins [23].

Analytical, diagnostic and therapeutic context of LMNB2

• The origin was localized, by means of quantitative PCR within approximately 3000 bp, in a highly transcribed region containing at least two closely spaced genes with the same polarity of transcription, one encoding lamin B2 and the other an unidentified protein [24].
• As assayed by both fluorescence observing and quantitative RT-PCR, the protein and mRNA products of exogenous gene RFP were efficiently and specifically inhibited; quantitative RT-PCR and western blotting results respectively demonstrated that endogenous lamin B2 mRNA and protein was suppressed without global down-regulation of protein synthesis [25].

References