標題: Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response
作者: Shih, Jing-Wen
Wang, Wei-Ting
Tsai, Tsung-Yuan
Kuo, Chu-Yun
Li, Hao-Kang
Lee, Yan-Hwa Wu
生物科技學系
Department of Biological Science and Technology
關鍵字: DEAD box RNA helicase;DDX3;eukaryotic initiation factor 4E-inhibitory protein (eIF4E-inhibitory protein);processing body;stress granule;stress response
公開日期: 1-一月-2012
摘要: Upon environmental insults, SGs (stress granules) aid cell survival by serving as sites of translational silencing. RNA helicase DDX3 was reported to associate with SGs. However, its role in SG physiology remains undefined. We have demonstrated previously that DDX3 acts as an eIF4E (eukaryotic initiation factor 4E)-inhibitory protein to suppress translation. In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. We established various stimuli as novel stressors that direct DDX3 with eIF4E and PABP1 into SGs, but not to processing bodies. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival. Notably, the SG-inducing capacity of DDX3 is independent of its ATPase and helicase activities, but mapped to the eIF4E-binding region. Moreover, the eIF4E-binding-defective mutant DDX3 was impaired in its SG-inducing ability and protective effect on cell survival under adverse conditions. All together, the present study has characterized DDX3 as a pivotal SG-nucleating factor and illustrates co-ordinative roles for DDX3, eIF4E and PABP1 in integrating environmental stress with translational regulation.
URI: http://dx.doi.org/10.1042/BJ20110739
http://hdl.handle.net/11536/15307
ISSN: 0264-6021
DOI: 10.1042/BJ20110739
期刊: BIOCHEMICAL JOURNAL
Volume: 441
Issue: 
起始頁: 119
結束頁: 129
顯示於類別:期刊論文


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