PMID- 24910119
OWN - NLM
STAT- MEDLINE
DCOM- 20140922
LR  - 20211021
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 281
IP  - 15
DP  - 2014 Aug
TI  - Aberrant sumoylation signaling evoked by reactive oxygen species impairs 
      protective function of Prdx6 by destabilization and repression of its 
      transcription.
PG  - 3357-81
LID - 10.1111/febs.12866 [doi]
AB  - Loss of the cytoprotective protein peroxiredoxin 6 (Prdx6) in cells that are 
      aging or under oxidative stress is known to be linked to the 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 lens epithelial cells (LECs) facing oxidative 
      stress and aging lenses, we found a significant increase in the levels of small 
      ubiquitin-like modifier (Sumo)1 conjugates. These cells displayed increased 
      levels of Sumo1 and reduced the 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 specificity 
      protein 1 (Sp1), mRNA and protein with increased levels of reactive oxygen 
      species; 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 Sumo-specific protease (Senp)1. Experiments with Sumo1-fused Prdx6 
      and Prdx6 promoter-linked to chloramphenicol acetyltransferase reporter gene 
      constructs indicated that Sumo1 dysregulated Prdx6 activity by reducing its 
      abundance and attenuating its transcription; in contrast, the delivery of Senp1 
      or Prdx6 reversed the process. The data show that reactive oxygen species-evoked 
      aberrant sumoylation signaling affects Prdx6 activity by reducing Prdx6 
      abundance, as well as transcription. The findings of the present study may 
      provide a foundation for a strategy to repair deleterious oxidative signaling 
      generated by a reduced activity of Prdx6.
CI  - (c) 2014 FEBS.
FAU - Chhunchha, Bhavana
AU  - Chhunchha B
AD  - Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, 
      NE, USA.
FAU - Fatma, Nigar
AU  - Fatma N
FAU - Kubo, Eri
AU  - Kubo E
FAU - Singh, Dhirendra P
AU  - Singh DP
LA  - eng
GR  - R01 EY024589/EY/NEI NIH HHS/United States
GR  - R01 EY017613/EY/NEI NIH HHS/United States
GR  - R01 EY013394/EY/NEI NIH HHS/United States
GR  - EY017613/EY/NEI NIH HHS/United States
GR  - EY013394/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140701
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (SUMO-1 Protein)
RN  - 0 (SUMO1 protein, human)
RN  - 0 (Sp1 Transcription Factor)
RN  - EC 1.11.1.15 (PRDX6 protein, human)
RN  - EC 1.11.1.15 (Peroxiredoxin VI)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.- (SENP1 protein, human)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Aging
MH  - Animals
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cysteine Endopeptidases
MH  - Endopeptidases/genetics/metabolism
MH  - Enzyme Repression
MH  - Enzyme Stability
MH  - Humans
MH  - Mice
MH  - Oxidative Stress
MH  - Peroxiredoxin VI/*physiology
MH  - Reactive Oxygen Species/*metabolism
MH  - SUMO-1 Protein/*metabolism
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/genetics/metabolism
MH  - *Sumoylation
MH  - *Transcription, Genetic
PMC - PMC4474172
MID - NIHMS603154
OTO - NOTNLM
OT  - Prdx6
OT  - Senp1
OT  - Sumo1
OT  - cell survival
OT  - oxidative stress
EDAT- 2014/06/10 06:00
MHDA- 2014/09/23 06:00
PMCR- 2015/08/01
CRDT- 2014/06/10 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/05/24 00:00 [revised]
PHST- 2014/06/05 00:00 [accepted]
PHST- 2014/06/10 06:00 [entrez]
PHST- 2014/06/10 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - 10.1111/febs.12866 [doi]
PST - ppublish
SO  - FEBS J. 2014 Aug;281(15):3357-81. doi: 10.1111/febs.12866. Epub 2014 Jul 1.