Benign anomaly to malign dysplasia: Variable expression of lamin B receptor mutations in humans

摘要

Ten years ago, K G Papavinasasundaram, then a post-doc in my lab, discovered that the Neurospora sterol biosynthetic enzyme C-14 sterol reductase, had a sequence that was very similar to that of the C-terminal ～ 450 residues of the lamin B receptor (LBR), a ～ 630 residue integral protein of the vertebrate inner nuclear membrane (Papavinasasundaram and Kasbekar 1994). The N-terminal ～ 180 residues of LBR are nucleoplasmic, associate with the nuclear lamina and heterochromatin, and are believed to play an important role in maintaining nuclear architecture. My student Prakash Arumugam showed subsequently that the human LBR C-terminal domain could complement a Neurospora C-14 sterol reductase mutant and thus established its C-14 sterol reductase function (Prakash et al 1999). Subsequent studies by Prakash focused on a paralog of the LBR C-terminal domain encoded by the TM7SF2 gene.