Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted.
Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted.
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DOI：
10.1016/j.bbrc.2009.12.090
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发表时间：
2010-01-15
影响因子：
3.1
通讯作者：
Bell, Graeme I.
中科院分区：
文献类型：
--
作者：
Park, Soo-Young;Ye, Honggang;Steiner, Donald F.;Bell, Graeme I.
影响前胰岛素原加工成胰岛素原或导致胰岛素原错误折叠的前胰岛素原蛋白突变与糖尿病有关。我们检测了 13 种新生儿糖尿病相关人胰岛素原蛋白（A24D、G32R、G32S、L35P、C43G、G47V、F48C、G84R、R89C、G90C、C96Y、S101C 和 Y108C）在大鼠 INS-1 胰岛素瘤细胞中的亚细胞定位和分泌。这些突变型胰岛素原蛋白在内质网 (ER) 中积累，除 G84R 外，其分泌性较差，与野生型和高胰岛素原血症相关的突变型蛋白（H34D 和 R89H）相反，后者被分选为分泌颗粒并有效分泌。我们还检查了 C96Y 突变型胰岛素原对野生型胰岛素合成和分泌的影响，并观察到突变型胰岛素原由于诱导未折叠蛋白反应并导致整体翻译减弱而对野生型胰岛素合成和分泌产生显性负效应。
Mutations in the preproinsulin protein that affect processing of preproinsulin to proinsulin or lead to misfolding of proinsulin are associated with diabetes. We examined the subcellular localization and secretion of 13 neonatal diabetes-associated human proinsulin proteins (A24D, G32R, G32S, L35P, C43G, G47V, F48C, G84R, R89C, G90C, C96Y, S101C and Y108C) in rat INS-1 insulinoma cells. These mutant proinsulin proteins accumulate in the endoplasmic reticulum (ER) and are poorly secreted except for G84R and in contrast to wild-type and hyperproinsulinemia-associated mutant proteins (H34D and R89H) which were sorted to secretory granules and efficiently secreted. We also examined the effect of C96Y mutant proinsulin on the synthesis and secretion of wild-type insulin and observed a dominant-negative effect of the mutant proinsulin on the synthesis and secretion of wild-type insulin due to induction of the unfolded protein response and resulting attenuation of overall translation.
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人类胰岛素基因的七种突变与永久性新生儿/婴幼儿糖尿病有关
影响因子：
15.9
作者：
Colombo, Carlo;Porzio, Ottavia;Barbetti, Fabrizio
通讯作者：
Barbetti, Fabrizio
影响因子：
4.8
作者：
Ohara-Imaizumi, M;Nakamichi, Y;Nagamatsu, S
通讯作者：
Nagamatsu, S
DOI：
10.1073/pnas.0702697104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Liu, Ming;Hodish, Israel;Arvan, Peter
通讯作者：
Arvan, Peter
影响因子：
64.8
作者：
BELL, GI;SWAIN, WF;RUTTER, WJ
通讯作者：
RUTTER, WJ
影响因子：
3.5
作者：
Rubio-Cabezas, O.;Edghill, E. L.;Hattersley, A. T.
通讯作者：
Hattersley, A. T.