June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Protein Serine/Threonine Phosphatases Dephosphorylate CREB at S133 and Regulates Lens Differentiation, Apoptosis and Anastasis
Author Affiliations & Notes
  • David W Li
    Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska, United States
    The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of SUn Yat-Sen University, Guangzhou, Guangdong, China
  • Ling Wang
    The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of SUn Yat-Sen University, Guangzhou, Guangdong, China
  • Xiao-Hui Hu
    Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Zhao-Xia Huang
    Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • James W Gigantelli
    Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Quan Dong Nguyen
    Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Footnotes
    Commercial Relationships   David Li, None; Ling Wang, None; Xiao-Hui Hu, None; Zhao-Xia Huang, None; James Gigantelli, None; Quan Nguyen, None
  • Footnotes
    Support  NSFC-81570824
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1713. doi:
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      David W Li, Ling Wang, Xiao-Hui Hu, Zhao-Xia Huang, James W Gigantelli, Quan Dong Nguyen; Protein Serine/Threonine Phosphatases Dephosphorylate CREB at S133 and Regulates Lens Differentiation, Apoptosis and Anastasis
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):1713.

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

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Abstract

Purpose : CREB is one of the major transcription factors implicated in regulating lens differentiation and pathogenesis. Knockout of its close family member, CREB-2 (ATF4) leads to massive apoptosis in the developing lens followed by cataractogenesis. The functions of CREB are regulated by various protein kinases via Ser-133. Previous studies have shown that CREB is also regulated by PP-2A. In the present studies, we have further characterized regulation of CREB functions by PP-1 mediated dephosphorylation at Ser-133.

Methods : Human lens epithelial cells and aTN4-1 mouse lens epithelial cells were used as testing systems. Co-immunoprecipitation assays, in vitro dephosphorylation assay, inhibition of phosphatase activity, overexpression and knockdown of various subunits from PP-1 and PP-2A were used to determine the specific dephosphorylation of CREB by PP-1 and PP-2A. Reverse transcription polymerase chain reaction, Western-blot analysis and reporter gene activity assays were used to study gene expression under CREB regulation.

Results : Lens epithelial cells undergoing apoptosis induced by stress conditions can be reversed as the stress conditions are removed, a condition called anastasis. Wild type CREB, and its phosphorylation mutant as well as dephosphorylation mutant display significantly different functions in regulating both apoptosis and anastasis.

Conclusions : Both PP-1 and PP-2A can directly dephosphorylate CREB to regulate lens differentiation via control of both apoptosis and anastasis. Both apoptosis and anastasis are implicated in modulating lens differentiation (Supported by Research Prevent Blindness, NSFC-81570824, Zhongshan Ophthalmic Center, and Chinese Scholarship Council).

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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