Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated transcription activation of nuclear gene targets.
Role of calcineurin, hnRNPA2 and Akt in mitochondrial respiratory stress-mediated transcription activation of nuclear gene targets.
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DOI：
10.1016/j.bbabio.2010.02.008
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发表时间：
2010-06
影响因子：
4.3
通讯作者：
Avadhani, Narayan G.
中科院分区：
文献类型：
--
作者：
Guha, Manti;Tang, Weigang;Sondheimer, Neal;Avadhani, Narayan G.
关键词：
Pathophysiological conditions causing mitochondrial dysfunction and altered transmembrane potential (Δψm) initiate a mitochondrial respiratory stress response, also known as mitochondrial retrograde response, in a variety of mammalian cells. An increase in the cytosolic Ca2+ [Ca2+]c as part of this signaling cascade activates Ca2+ responsive phosphatase, Calcineurin (Cn). Activation of IGF1R accompanied by increased glycolysis, invasiveness, and resistance to apoptosis are phenotypic hallmarks of C2C12 rhabdomyoblast cells subjected to this stress. The signaling is associated with activation and increased nuclear translocation of a number of transcription factors including a novel NFκB (cRel: p50) pathway, NFAT, CREB and C/EBPδ. This culminates in the upregulation of a number of nuclear genes including Cathepsin L, RyR1, Glut4 and Akt1. We observed that stress regulated transcription activation of nuclear genes involves a cooperative interplay between NFκB (cRel:p50), C/EBPδ, CREB, NFAT. Our results show that the functional synergy of these factors requires the stress-activated heterogeneous nuclear ribonucleoprotein, hnRNPA2 as a transcriptional co-activator. We report here that mitochondrial stress leads to induced expression and activation of serine threonine kinase Akt1. Interestingly, we observe that Akt1 phosphorylates hnRNPA2 under mitochondrial stress conditions, which is a crucial step for the recruitment of this coactivator to the stress target promoters and culmination in mitochondrial stress-mediated transcription activation of target genes. We propose that mitochondrial stress plays an important role in tumor progression and emergence of invasive phenotypes.
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影响因子：
3.3
作者：
Guha, Manti;Pan, Hua;Avadhani, Narayan G.
通讯作者：
Avadhani, Narayan G.
影响因子：
11.4
作者：
Biswas, G;Adebanjo, OA;Avadhani, NG
通讯作者：
Avadhani, NG
DOI：
10.1083/jcb.200211104
发表时间：
2003-05-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Biswas G;Anandatheerthavarada HK;Zaidi M;Avadhani NG
通讯作者：
Avadhani NG
影响因子：
4.8
作者：
Guha, Manti;Srinivasan, Satish;Avadhani, Narayan G.
通讯作者：
Avadhani, Narayan G.
影响因子：
4.8
作者：
Buratti, E;Brindisi, A;Baralle, FE
通讯作者：
Baralle, FE