June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The Function of the E3 Ligase, MDM2 Is Subjected to Dephosphorylation Regulation by Protein Serine/Threonine Phosphatase-1 and -2A
Author Affiliations & Notes
  • Wenfeng Hu
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    Key Laboratory of Protein Chemistry and Developmental Biology, College of Life Science, Hunan Normal University, Changsha, China
  • Xiao-Hui Hu
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    Key Laboratory of Protein Chemistry and Developmental Biology, College of Life Science, Hunan Normal University, Changsha, China
  • Weike Ji
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE
  • Mi Deng
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE
  • Zachary Woodward
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE
  • David Li
    Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE
    Key Laboratory of Protein Chemistry and Developmental Biology, College of Life Science, Hunan Normal University, Changsha, China
  • Footnotes
    Commercial Relationships Wenfeng Hu, None; Xiao-Hui Hu, None; Weike Ji, None; Mi Deng, None; Zachary Woodward, None; David Li, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 477. doi:
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      Wenfeng Hu, Xiao-Hui Hu, Weike Ji, Mi Deng, Zachary Woodward, David Li; The Function of the E3 Ligase, MDM2 Is Subjected to Dephosphorylation Regulation by Protein Serine/Threonine Phosphatase-1 and -2A. Invest. Ophthalmol. Vis. Sci. 2013;54(15):477.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Stress-induced apoptosis of lens epithelial cells plays an important role during stress-induced cataractogenesis. As the major serine/threonine phosphatases, our previous studies have shown that PP-1 and PP-2A are implicated in regulation of p53 functions and thus participate in the control of p53-mediated apoptosis. On the other hand, the stability of p53 is regulated by the E3 ligase, MDM2. Whether PP-1 or PP-2A directly regulates the function of MDM2 through dephosphorylation to control p53 functions remains largely unknown. The present study investigates the dephosphorylation regulation of MDM2 functions by PP-1 and PP-2A.

Methods: Human lens epithelial cells, alphaTN4-1 mouse lens epithelial cells, wild type and p53 knockout mice were used as testing systems. Lens epithelial cells or organ cultures were subjected to different oxidative stress conditions. Co-immunoprecipitation assays were used to investigate the interaction between MDM2 and PP-1/-2A. Immunofluroescence was used to detect the expression patterns of MDM2 in embryonic lens from wild type and p53 knockout mice. QRT-PCR and Western-blot analysis were used to study the activation of MDM2 signaling pathway under various conditions of PP-1/-2A expression (overexpression and knockdown).

Results: In the p53 knockout mice, expression of MDM2 was significantly decreased during embryonic development of mouse lens. Both PP-1 and PP-2A can dephosphorylate MDM2 as demonstrated from Co-IP between MDM2 and PP-1/-2A, and overexpression and knockdown of PP-1 and -2A.

Conclusions: PP-1 and -2A directly dephosphorylate MDM2 to modulate its interaction with p53 and thus regulate oxidative stress-induced apoptosis of lens epithelial cells. (Supported by EY018380, CSC and HNU)

Keywords: 426 apoptosis/cell death • 646 phosphorylation • 445 cataract  
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