Disease relevance of Lmnb1

• The DNA region established stable associations with nuclear lamin B (67 kDa, pI 5.7) in the controls, and with lamins A (69 kDa, pI 7.0), B, isoforms of lamin C (62 kDa, pI 6.55-6.95), and a 55-kDa (pI 5.9) polypeptide during the acute phase response [1].

High impact information on Lmnb1

• The LAPs are phosphorylated during mitosis, and phosphorylation of LAP 2 by mitotic cytosol inhibits its binding to both lamin B1 and chromosomes [2].
• By means of a DNA-binding protein blot assay and in vitro binding studies, we identified lamin B1 as a MAR-binding protein, which provides evidence for a specific interaction of DNA with the nuclear lamina [3].
• Binding of matrix attachment regions to lamin B1 [3].
• Lamina-associated polypeptide 2 (LAP2) is an integral membrane protein of the inner nuclear membrane, which binds directly to both lamin B1 and chromosomes in a mitotic phosphorylation-regulated manner [4].
• Presence of a protein immunologically related to lamin B in the postsynaptic membrane of Torpedo marmorata electrocyte [5].

Biological context of Lmnb1

• They also indicate that cAMP-dependent phosphorylation of interphase lamin B could cause remodeling of the lamina and establishment of homopolymeric domains [6].
• Resistance correlated with a reduced ability of L-739,749 to inhibit the farnesylation of Ras and lamin B and with a reduction in the susceptibility of endogenous FT to drug inhibition [7].
• Protein kinase C-mediated interphase lamin B phosphorylation and solubilization [8].
• Lamin B of permeabilized sea urchin sperm nuclei incubated in fertilized egg G1 phase cytosolic extract is phosphorylated within 1 min of incubation and solubilized prior to sperm chromatin decondensation [8].
• Both the nuclear mitotic apparatus protein and lamin B were specifically targeted by protease(s) at early stages of the cell death pathway, which possibly initiate the cascade of degradative events in apoptosis [9].

Anatomical context of Lmnb1

• These findings would represent an extension of the model proposed by Georgatos and Blobel (Georgatos, S. D., and G. Blobel. 1987a. J. Cell Biol. 105:105-115) in which type III intermediate size filaments are vectorially inserted to plasma and nuclear membranes by ankyrin and lamin B, respectively [5].
• In this work, we show that polyclonal antibodies specific for lamin B recognizes a component of the plasma membrane of Torpedo electrocyte [5].
• 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 [10].
• Disappearance of NUP153 and lamin B was coincident with onset of DNA fragmentation and clustering of nuclear pores [11].
• The elevation of nuclear proteolytic activity was accompanied by site-specific degradation of nuclear mitotic apparatus protein and lamin B, two essential components of the nuclear matrix [9].

Associations of Lmnb1 with chemical compounds

• After purification of the lamins from such urea extracts, a specific binding between isolated vimentin and lamin B, or a lamin A + B hetero-oligomer, was detected by affinity chromatography [12].
• The location of lamin B as an intrinsic membrane protein was also established by photoaffinity labeling with the membrane-penetrating reagent azidopyrene [10].
• Lithium pretreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3 [13].
• Cleavage of lamin B, which generated a fragment of 46 kDa consistent with the central rod domain of the protein, was also detected after 30 minutes of exposure to the steroid hormone [9].
• The level of lamin B phosphorylation did not change as a result of the dexamethasone treatment and the lamina did not solubilize until the later stages of apoptosis [9].

Regulatory relationships of Lmnb1

• Interleukin-1 beta induces posttranslational carboxymethylation and alterations in subnuclear distribution of lamin B in insulin-secreting RINm5F cells [14].

Other interactions of Lmnb1

• Activation of intracellular caspases, manifest by proteolytic poly (ADP-ribose) polymerase (PARP) and lamin B cleavage, was maximal at 15 h after IR, concident with other indices of EC apoptosis, including oligonucleosomal DNA degradation, TUNEL immunostaining, and morphologic changes [15].
• By other approaches (quantitative immunoprecipitation, rate zonal sedimentation, turbidometric assays) a substoichiometric lamin B-vimentin binding was determined under in vitro conditions [12].
• 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 [6].
• Upon Te treatment, no degradation of the caspase substrates poly (ADP-ribose) polymerase and lamin B was detected by Western blots or immunocytochemistry, respectively [16].
• With this in mind, we have used immunogold labeling to examine the topological associations of desmin cytoskeletal and lamin B nucleoskeletal intermediate filaments with various intracellular structures in mammalian cardiac myocytes [17].

Analytical, diagnostic and therapeutic context of Lmnb1

• This conclusion was based on (a) transmission electron microscopy, (b) lipid analysis, (c) lamin B as an inner membrane-associated marker, and (d) the demonstration of phospholipid lateral mobility on outer membrane-depleted nuclei as a criteria for inner membrane integrity [18].
• When hepatocytes were stimulated to divide by partial hepatectomy, only synthesis of lamin B was initiated [19].
• For gel electrophoresis and Western blotting, we used antibodies to poly (ADP-ribose) polymerase (PARP), lamin B, and PKC-delta, as specific cleavage substrates of caspases [20].
• The lamina structure of pre-meiotic spermatogonial nucleus contains both somatic lamin B and lamin(g) as evidenced by immunofluorescence studies with two differently fluorochrome labelled anti-lamin B and anti-lamin(g) antibodies [21].
• In proliferating cells (tumors, regenerating liver, log phase cell culture) a polypeptide band of 150 kD and lamin B were conspicuous at the expense of lamins A and C [22].

References