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RISS 인기검색어
- 검색키워드
- 저자 : ( Deepika Vasudevan ) (검색결과 2 건)
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4E-BP is a target of the GCN2–ATF4 pathway during <i>Drosophila</i> development and aging
Kang, Min-Ji,Vasudevan, Deepika,Kang, Kwonyoon,Kim, Kyunggon,Park, Jung-Eun,Zhang, Nan,Zeng, Xiaomei,Neubert, Thomas A.,Marr II, Michael T.,Ryoo, Hyung Don The Rockefeller University Press 2017 The Journal of cell biology Vol.216 No.1
<P>Reduced amino acid availability attenuates mRNA translation in cells and helps to extend lifespan in model organisms. The amino acid deprivation activated kinase GCN2 mediates this response in part by phosphorylating elF2 alpha. In addition, the cap-dependent translational inhibitor 4E-BP is transcriptionally induced to extend lifespan in Drosophila melanogaster, but through an unclear mechanism. Here, we show that GCN2 and its downstream transcription factor, ATF4, mediate 4E-BP induction, and GCN2 is required for lifespan extension in response to dietary restriction of amino acids. The 4E-BP intron contains ATF4-binding sites that not only respond to stress but also show inherent ATF4 activity during normal development. Analysis of the newly synthesized proteome through metabolic labeling combined with click chemistry shows that certain stress-responsive proteins are resistant to inhibition by 4E-BP, and gcn2 mutant flies have reduced levels of stress-responsive protein synthesis. These results indicate that GCN2 and ATF4 are important regulators of 4E-BP transcription during normal development and aging.</P>
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Two distinct nodes of translational inhibition in the Integrated Stress Response
( Hyung Don Ryoo ),( Deepika Vasudevan ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.11
The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated eIF2α kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor eIF2α. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes. [BMB Reports 2017; 50(11): 539-545]
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