The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner.
The nuclear mitotic apparatus protein NuMA controls rDNA transcription and mediates the nucleolar stress response in a p53-independent manner.
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核有丝分裂装置蛋白 NuMA 控制 rDNA 转录，并以不依赖 p53 的方式介导核极应激反应。
DOI：
10.1093/nar/gkx782
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发表时间：
2017-11-16
影响因子：
14.9
通讯作者：
Lelièvre SA
中科院分区：
文献类型：
--
作者：
Jayaraman S;Chittiboyina S;Bai Y;Abad PC;Vidi PA;Stauffacher CV;Lelièvre SA
核有丝分裂器蛋白NuMA参与主要的细胞事件，如DNA损伤反应、细胞凋亡和p53介导的生长停滞，所有这些都在应激时受核仁控制。蛋白质组学研究已经在数百种核仁蛋白中鉴定出NuMA。然而，NuMA和核仁功能之间的确切联系仍然不确定。我们证实，NuMA是存在于核仁中，并揭示重新分配的NuMA放线菌素D或阿霉素诱导的核仁应力。NuMA与RNA聚合酶I、核糖体蛋白RPL 26和RPL 24以及与rDNA转录相关的ATP依赖性染色质重塑复合物B-WICH的组分共免疫沉淀。NuMA还结合18 S和28 S rRNA并定位于rDNA启动子区。NuMA表达的下调触发核仁应激，如通过减少的新生前rRNA合成、原纤维蛋白核仁周帽形成和p27 kip 1而不是p53的上调所示。生理相关的核仁应激诱导与活性氧重申了p53-独立的p27 kip 1反应途径，并导致新生前rRNA减少。它还促进了NuMA量的减少。NuMA在rDNA转录和p53非依赖性核仁应激反应中的这种先前未表征的功能支持这种核结构蛋白在细胞内稳态中的核心作用。
The nuclear mitotic apparatus protein, NuMA, is involved in major cellular events such as DNA damage response, apoptosis and p53-mediated growth-arrest, all of which are under the control of the nucleolus upon stress. Proteomic investigation has identified NuMA among hundreds of nucleolar proteins. Yet, the precise link between NuMA and nucleolar function remains undetermined. We confirm that NuMA is present in the nucleolus and reveal redistribution of NuMA upon actinomycin D or doxorubicin-induced nucleolar stress. NuMA coimmunoprecipitates with RNA polymerase I, with ribosomal proteins RPL26 and RPL24, and with components of B-WICH, an ATP-dependent chromatin remodeling complex associated with rDNA transcription. NuMA also binds to 18S and 28S rRNAs and localizes to rDNA promoter regions. Downregulation of NuMA expression triggers nucleolar stress, as shown by decreased nascent pre-rRNA synthesis, fibrillarin perinucleolar cap formation and upregulation of p27kip1, but not p53. Physiologically relevant nucleolar stress induction with reactive oxygen species reaffirms a p53-independent p27kip1 response pathway and leads to nascent pre-rRNA reduction. It also promotes the decrease in the amount of NuMA. This previously uncharacterized function of NuMA in rDNA transcription and p53-independent nucleolar stress response supports a central role for this nuclear structural protein in cellular homeostasis.
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影响因子：
--
作者：
Esposito D;Crescenzi E;Sagar V;Loreni F;Russo A;Russo G
通讯作者：
Russo G
DOI：
10.1083/jcb.120.4.947
发表时间：
1993-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Compton DA;Cleveland DW
通讯作者：
Cleveland DW
影响因子：
9.2
作者：
Andersen, JS;Lyon, CE;Lamond, AI
通讯作者：
Lamond, AI
影响因子：
3.3
作者：
Abad, Patricia C.;Lewis, Jason;Lelievre, Sophie A.
通讯作者：
Lelievre, Sophie A.
DOI：
10.1007/bf02623578
发表时间：
1987-03-01
期刊：
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY
影响因子：
--
作者：
BRIAND, P;PETERSEN, OW;VANDEURS, B
通讯作者：
VANDEURS, B