LMNB1

LMNB1 Background

The human gene LMNB1 encodes nuclear lamin B1, an intermediate filament protein of the nuclear envelope ^[1]. LMNB1 contains an N-terminal head domain, a conserved α-helical central rod domain, and a C-terminal tail domain ^[1]. All lamins share the common central rod domain flanked by globular head and tail domains ^[2]. At least one of the B-type lamins is expressed in all cells throughout development ^[2]. LMNB1, along with heterochromatin, is anchored to the inner surface of the nuclear membrane by the lamin B receptor. The study of Takeshi Shimi et al. showed that silencing LMNB1 expression slows proliferation and rapidly induces premature senescence ^[3]. The reduction of its expression during senescence is mediated by pRb ^[3]. On the other hand, the overexpression of GFP-LMNB1 increases the proliferation rate and delays the onset of senescence of human diploid fibroblasts (HDFs) ^[3]. LMNB1 regulates proliferation and senescence of human diploid cells through a ROS signaling pathway ^[3]. By 3D-FISH, Camps J et al. identified a central role of LMNB1 for the condensation of chromosome territories, for the distribution of heterochromatin, and the regulation of gene expression and splicing ^[4]. The only known disease involving LB1 is adult-onset autosomal dominant leukodystrophy (ADLD), a progressive demyelinating disease caused by the overexpression of LB1 in neurons because of either gene duplication or a mutation in the LMNB1 promoter ^[5]. Studies of mouse models made null for LMNB1 expression or expressing a truncated form of LMNB1 show defects in organogenesis, especially of the brain ^[6][7].

[1] Lin F, Worman HJ et al. Structural organization of the human gene (LMNB1) encoding nuclear lamin B1 [J]. Genomics. 1995, 27 (2): 230-6.
[2] Dechat T, Pfleghaar K, et al. Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin [J]. Genes Dev. 2008 Apr 1; 22(7):832-53.
[3] Takeshi Shimi, Veronika Butin-Israeli, et al. The role of nuclear lamin B1 in cell proliferation and senescence [J]. Genes Dev. 2011 Dec 15; 25(24): 2579-2593.
[4] Camps J, Erdos MR, et al. The role of lamin B1 for the maintenance of nuclear structure and function [J]. Nucleus. 2015;6(1):8-14.
[5] Padiath QS, Saigoh K, et al. Lamin B1 duplications cause autosomal dominant leukodystrophy [J]. Nat Genet 2006, 38:1114-1123.
[6] Coffinier C, Jung HJ, et al. Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons [J]. Mol Biol Cell 2011, 22:4683-4693.
[7] Kim Y, Sharov AA, et al. Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells [J]. Science 2011, 334:1706-1710.