The molecular aetiology of the serpinopathies

被引：29

作者：

Davies, Mark J. ^{[1
]}

Lomas, David A. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Med, Cambridge Inst Med Res, Cambridge CB2 0XY, England

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2008年 / 40卷 / 6-7期

基金：

英国医学研究理事会;

关键词：

alpha(1)-antitrypsin; neuroserpin; proteinase inhibitor; serpin; conformational disease;

D O I：

10.1016/j.biocel.2007.12.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Members of the serine proteinase inhibitor or serpin superfamily inhibit their target proteinases by a conformational transition that involves the enzyme being translocated from the upper to the lower pole of the protein. This sophisticated mechanism is subverted by point mutations to form ordered polymers that are retained within the endoplasmic reticulum of the cell of synthesis. These polymers activate NF-kappa B and cause cytotoxicity by a pathway that is independent of the unfolded protein response. As diverse conditions can be explained the same mechanism of polymerisation we have grouped them together as a new class of disease, the serpinopathies. We review here the structural basis of the serpinopathies and discuss how the ordered accumulation of polymers causes cell death. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1273 / 1286

页数：14

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