Aberrant sumoylation signaling evoked by reactive oxygen species impairs protective function of Prdx6 by destabilization and repression of its transcription.
Aberrant sumoylation signaling evoked by reactive oxygen species impairs protective function of Prdx6 by destabilization and repression of its transcription.
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DOI：
10.1111/febs.12866
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Singh DP
中科院分区：
文献类型：
--
作者：
Chhunchha B;Fatma N;Kubo E;Singh DP
Loss of the cytoprotective protein Peroxiredoxin 6 (Prdx6) in cells that are aging or under oxidative stress is known to be linked to pathobiology of many age-related diseases. However, the mechanism by which Prdx6 activity goes awry is largely unknown. Using Prdx6-deficient (Prdx6−/−) cells as a model for aging or redox active cells, human/mouse LECs facing oxidative stress, and aging lenses, we found a significant increase in the levels of Sumo1 conjugates. These cells displayed increased levels of Sumo1 and reduced expression of Prdx6. Specifically we observed that Prdx6 is a target for aberrant Sumoylation signaling, and that Sumo1 modification reduces its cellular abundance. LECs overexpressing Sumo1 showed reduced expression and activity of Prdx6 and its transactivator Sp1, mRNA and protein with increased levels of ROS; those cells were vulnerable to oxidative stress-induced cell death. A significant reduction in Prdx6, Sp1 protein and mRNA expression was observed in redox-active Prdx6−/− cells and in aging lenses/LECs. The reduction was correlated with increased expression of Sumo1 and enrichment of the inactive form (dimeric) of Sumo1 specific protease Senp1. Experiments with Sumo1-fused Prdx6 and Prdx6 promoter-linked to CAT reporter gene constructs pointed that Sumo1 dysregulated Prdx6 activity by reducing its abundance and attenuating its transcription, in contrast delivery of Senp1 or Prdx6 reversed the process. Data underpins that ROS-evoked aberrant Sumoylation signaling affects Prdx6 activity by reducing Prdx6 abundance as well as transcription. Our finding may provide a foundation for a strategy to repair deleterious oxidative signaling generated by reduced activity of Prdx6.
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影响因子：
3.3
作者：
Fatma N;Kubo E;Toris CB;Stamer WD;Camras CB;Singh DP
通讯作者：
Singh DP
影响因子：
21.3
作者：
Dadke, Shrikrishna;Cotteret, Sophie;Chernoff, Jonathan
通讯作者：
Chernoff, Jonathan
DOI：
10.1016/j.bbrc.2006.06.092
发表时间：
2006-08-25
影响因子：
3.1
作者：
Fei, Erkang;Jia, Nali;Wang, Guanghui
通讯作者：
Wang, Guanghui
影响因子：
16
作者：
Bossis, G;Melchior, F
通讯作者：
Melchior, F
影响因子：
3.7
作者：
Chen X;Ding B;LeJeune D;Ruggiero C;Li S
通讯作者：
Li S