PMID- 22684029
OWN - NLM
STAT- MEDLINE
DCOM- 20121030
LR  - 20211021
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 33
IP  - 7
DP  - 2012 Jul
TI  - The biphasic redox sensing of SENP3 accounts for the HIF-1 transcriptional 
      activity shift by oxidative stress.
PG  - 953-63
LID - 10.1038/aps.2012.40 [doi]
AB  - AIM: To investigate the mechanisms underlying the biphasic redox regulation of 
      hypoxia-inducible factor-1 (HIF-1) transcriptional activity under different 
      levels of oxidative stress caused by reactive oxidative species (ROS). METHODS: 
      HeLa cells were exposed to different concentrations of H(2)O(2) as a simple model 
      for mild and severe oxidative stress. Luciferase reporter assay and/or 
      quantitative real-time PCR were used to investigate the transcriptional activity. 
      Immunoblot was used to detect protein expression. Chromatin immunoprecipitation 
      assay was used to detect HIF-1/DNA binding. The interaction of p300 with HIF-1alpha 
      or with SENP3, and the SUMO2/3 conjugation states of p300 were examined by 
      coimmunoprecipitation. RESULTS: HIF-1 transcriptional activity in HeLa cells was 
      enhanced by low doses (0.05-0.5 mmol/L) of H(2)O(2), but suppressed by high doses 
      (0.75-8.0 mmol/L) of H(2)O(2). The amount of co-activator p300 bound to HIF-1alpha in 
      HeLa cells was increased under mild oxidative stress, but decreased under severe 
      oxidative stress. The ROS levels differentially modified cysteines 243 and 532 in 
      the cysteine protease SENP3, regulating the interaction of SENP3 with p300 to 
      cause different SUMOylation of p300, thus shifting HIF-1 transcriptional 
      activity. CONCLUSION: The shift of HIF-1 transactivation by ROS is correlated 
      with and dependent on the biphasic redox sensing of SENP3 that leads to the 
      differential SENP3/p300 interaction and the consequent fluctuation in the p300 
      SUMOylation status.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Biochemistry and Molecular Cell Biology, Key Laboratory of the 
      Shanghai Science and Technology Commission for Cancer Microenvironment and 
      Inflammation, Institutes of Medical Sciences, Shanghai Jiao Tong University 
      School of Medicine, China.
FAU - Yang, Jie
AU  - Yang J
FAU - Yang, Kai
AU  - Yang K
FAU - Cang, Hui
AU  - Cang H
FAU - Huang, Xin-zhi
AU  - Huang XZ
FAU - Li, Hui
AU  - Li H
FAU - Yi, Jing
AU  - Yi J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120611
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (SUMO2 protein, human)
RN  - 0 (SUMO3 protein, human)
RN  - 0 (Small Ubiquitin-Related Modifier Proteins)
RN  - 0 (Ubiquitins)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.- (SENP3 protein, human)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Cysteine/metabolism
MH  - Cysteine Endopeptidases/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Hypoxia-Inducible Factor 1/*genetics/metabolism
MH  - Oxidation-Reduction
MH  - *Oxidative Stress
MH  - Reactive Oxygen Species/*metabolism
MH  - Small Ubiquitin-Related Modifier Proteins/metabolism
MH  - *Transcriptional Activation
MH  - Ubiquitins/metabolism
MH  - p300-CBP Transcription Factors/metabolism
PMC - PMC4011156
EDAT- 2012/06/12 06:00
MHDA- 2012/10/31 06:00
PMCR- 2012/07/01
CRDT- 2012/06/12 06:00
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2012/10/31 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - aps201240 [pii]
AID - 10.1038/aps.2012.40 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2012 Jul;33(7):953-63. doi: 10.1038/aps.2012.40. Epub 2012 
      Jun 11.