Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress.
Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress.
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DOI：
10.1093/nar/gkm753
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发表时间：
2007
影响因子：
14.9
通讯作者：
Van Dyck E
中科院分区：
文献类型：
--
作者：
Messaoudi L;Yang YG;Kinomura A;Stavreva DA;Yan G;Bortolin-Cavaillé ML;Arakawa H;Buerstedde JM;Hainaut P;Cavaillé J;Takata M;Van Dyck E
RDM1基因编码一个含有RNA识别基序(RRM)的蛋白质，参与脊椎动物对抗癌药物顺铂的细胞反应。我们先前报道了一个编码全长人类RDM1蛋白的cDNA。在这里，我们描述了11个人类编码RDM1蛋白亚型的cDNA的鉴定。这一谱系是通过交替的前mRNA剪接和两个翻译起始点的差异使用而产生的，导致蛋白质具有长或短的N-末端，其C-末端的外显子组成具有很大的多样性。通过使用标记蛋白和荧光显微镜，我们研究了全长RDM1(更名为RDM1RDM1α)和其他RDM1亚型的亚细胞分布。我们发现RDM1α在蛋白毒性应激和轻度热休克的响应下经历了亚细胞的重新分布和核仁的积累。在非应激细胞中，长N末端异构体表现出不同的亚细胞分布模式，从主要的细胞质定位到几乎唯一的核定位，这表明RDM1蛋白之间的功能差异。然而，所有的异构体都经历了应激诱导的核仁聚集。我们确定了核仁和核仁定位决定因素以及与RDM1蛋白的细胞质保留有关的区域。最后，RDM1缺失的鸡DT40细胞表现出比野生型(Wt)细胞更高的热休克敏感性，这表明RDM1在热休克反应中发挥了作用。
The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. This repertoire is generated by alternative pre-mRNA splicing and differential usage of two translational start sites, resulting in proteins with long or short N-terminus and a great diversity in the exonic composition of their C-terminus. By using tagged proteins and fluorescent microscopy, we examined the subcellular distribution of full-length RDM1 (renamed RDM1α), and other RDM1 isoforms. We show that RDM1α undergoes subcellular redistribution and nucleolar accumulation in response to proteotoxic stress and mild heat shock. In unstressed cells, the long N-terminal isoforms displayed distinct subcellular distribution patterns, ranging from a predominantly cytoplasmic to almost exclusive nuclear localization, suggesting functional differences among the RDM1 proteins. However, all isoforms underwent stress-induced nucleolar accumulation. We identified nuclear and nucleolar localization determinants as well as domains conferring cytoplasmic retention to the RDM1 proteins. Finally, RDM1 null chicken DT40 cells displayed an increased sensitivity to heat shock, compared to wild-type (wt) cells, suggesting a function for RDM1 in the heat-shock response.
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影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
5.3
作者：
Block, Gregory J.;Eskiw, Christopher H.;Bazett-Jones, David P.
通讯作者：
Bazett-Jones, David P.
影响因子：
3.3
作者：
Allemand, E;Dokudovskaya, S;Tazi, J
通讯作者：
Tazi, J
影响因子：
3.2
作者：
Calini, V;Urani, C;Camatini, M
通讯作者：
Camatini, M
影响因子：
4.8
作者：
Chatterjee, TK;Liu, ZY;Fisher, RA
通讯作者：
Fisher, RA