Hydrogen peroxide induces p16(INK4a) through an AUF1-dependent manner
Gai E Guo1, Li Wei Ma, Bin Jiang
1Department of Biochemistry, Changzhi Medical College, Changzhi, Shanxi 046000, PR China.
Journal of Cellular Biochemistry
|January 14, 2010
Summary
Hydrogen peroxide (H2O2) induces cellular senescence by increasing p16(INK4a) expression. RNA-binding protein AUF1 regulates this process by controlling p16(INK4a) mRNA turnover, revealing a novel senescence mechanism.
Area of Science:
- Molecular Biology
- Cellular Senescence
- Oxidative Stress
Background:
- p16(INK4a) elevation is a key factor in hydrogen peroxide (H2O2)-induced replicative senescence.
- The precise molecular mechanisms driving this p16(INK4a) upregulation remain largely unelucidated.
Purpose of the Study:
- To investigate the role of RNA-binding protein AUF1 in the regulation of p16(INK4a) expression during H2O2-induced senescence.
- To elucidate the mechanism of AUF1-mediated mRNA turnover in this cellular response.
Main Methods:
- Assessing cytoplasmic AUF1 levels and its binding to p16 3'UTR following H2O2 exposure.
- Utilizing chimeric transcripts (EGFP-p16-3'UTR) to measure mRNA half-life.
- Employing AUF1-silencing and overexpression strategies in HeLa cells.
Main Results:
- H2O2 treatment led to decreased cytoplasmic AUF1 levels and reduced AUF1 binding to p16 3'UTR.
- The half-life of p16 mRNA significantly increased under H2O2 conditions in a manner dependent on AUF1.
- AUF1 silencing abolished H2O2-induced p16 elevation, while AUF1 overexpression conferred resistance to H2O2-induced senescence.
Conclusions:
- AUF1 plays a critical role in mediating H2O2-induced p16(INK4a) expression.
- AUF1-dependent mRNA turnover is a crucial mechanism underlying cellular senescence induced by oxidative stress.
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