Stress granules contribute to α-globin homeostasis in differentiating erythroid cells.
Stress granules contribute to α-globin homeostasis in differentiating erythroid cells.
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DOI：
10.1016/j.bbrc.2012.03.070
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发表时间：
2012-04-20
影响因子：
3.1
通讯作者：
Anderson P
中科院分区：
文献类型：
--
作者：
Ghisolfi L;Dutt S;McConkey ME;Ebert BL;Anderson P
血红蛋白是红系细胞发育的主要生物合成产物。血红蛋白的组装需要平衡地产生球蛋白和携氧血红素部分。血红素调节抑制激酶（HRI）通过磷酸化eIF2α并在游离血红素水平受限时抑制球蛋白的翻译参与这一过程。HRI在受到氧化应激的红系细胞中也被激活。磷酸化eIF2 α介导的翻译抑制诱导应激颗粒（SG）的组装，这些颗粒是含有未翻译mRNA的细胞质病灶，并促进细胞在不利环境条件下的存活。我们已经发现，分化中的红细胞，但不是骨髓单核细胞或巨核细胞，鼠和人的祖细胞组装SG，在体外和体内。靶向敲低HRI或G3BP（SG组装所需的蛋白质）可抑制红系祖细胞中SG的自发和亚砷酸盐诱导组装。这伴随着珠蛋白产生减少和细胞凋亡增加，表明G3BP+ SG促进发育中的红系细胞的存活。
Hemoglobin is the major biosynthetic product of developing erythroid cells. Assembly of hemoglobin requires the balanced production of globin protein and the oxygen-carrying heme moiety. The heme-regulated inhibitor kinase (HRI) participates in this process by phosphorylating eIF2α and inhibiting the translation of globin protein when levels of free heme are limiting. HRI is also activated in erythroid cells subjected to oxidative stress. Phospho-eIF2α-mediated translational repression induces the assembly of stress granules (SG), cytoplasmic foci that harbor untranslated mRNAs and promote the survival of cells subjected to adverse environmental conditions. We have found that differentiating erythroid, but not myelomonocytic or megakaryocytic, murine and human progenitor cells assemble SGs, in vitro and in vivo. Targeted knockdown of HRI or G3BP, a protein required for SG assembly, inhibits spontaneous and arsenite-induced assembly of SGs in erythroid progenitor cells. This is accompanied by reduced globin production and increased apoptosis suggesting that G3BP+ SGs facilitate the survival of developing erythroid cells.
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影响因子：
20.3
作者：
Ebert, BL;Lee, MM;Sieff, CA
通讯作者：
Sieff, CA
影响因子：
21.3
作者：
Ohn, Takbum;Kedersha, Nancy;Hickman, Tyler;Tisdale, Sarah;Anderson, Paul
通讯作者：
Anderson, Paul
影响因子：
64.8
作者：
Ebert, Benjamin L.;Pretz, Jennifer;Bosco, Jocelyn;Chang, Cindy Y.;Tamayo, Pablo;Galili, Naomi;Raza, Azra;Root, David E.;Attar, Eyal;Ellis, Steven R.;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
5.3
作者：
Zekri, L;Chebli, K;Tazi, J
通讯作者：
Tazi, J
影响因子：
5.3
作者：
WEISS, IM;LIEBHABER, SA
通讯作者：
LIEBHABER, SA