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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity

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The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for

Han Lu1, Bin Liu, Fu-Jun Zhang

  • 1a Department of Anesthesiology ; Ruijin Hospital ; Shanghai Jiao-Tong University School of Medicine (SJTU-SM) ; Shanghai , People's Republic of China.

Cell Cycle (Georgetown, Tex.)
|December 9, 2014
PubMed

Insights

Activity-dependent stimuli regulate MEF2A transcription via the APC(Cdh1)-SENP2 axis. This pathway controls SENP2 stability and nuclear accumulation, promoting MEF2A deSUMOylation and acetylation for transcriptional activation.

Area of Science:

  • Molecular Biology
  • Transcriptional Regulation
  • Post-translational Modifications

Background:

  • MEF2A transcriptional activity is regulated by post-translational modifications like phosphorylation, SUMOylation, and acetylation.
  • SENP2, a deSUMOylating enzyme, was previously identified to promote MEF2A-dependent transcription.
  • The ubiquitin-proteasome system, particularly APC(Cdh1), plays a role in protein degradation.

Purpose of the Study:

  • To elucidate the role of the APC(Cdh1)-SENP2-MEF2A axis in regulating MEF2A transcriptional activation.
  • To investigate how activity-dependent stimuli influence this regulatory axis.
  • To define the post-transcriptional mechanisms controlling MEF2A activity.

Main Methods:

  • Co-immunoprecipitation to study protein interactions (APC(Cdh1) and SENP2).
  • Western blotting to detect ubiquitination and protein levels of SENP2 and MEF2A.
  • Immunofluorescence to assess SENP2 nuclear accumulation.
  • Analysis of MEF2A SUMOylation and acetylation states.

Main Results:

  • APC(Cdh1) targets SENP2 for ubiquitination and degradation in the cytoplasm via a D-box motif.
  • Activity-dependent stimuli inhibit APC(Cdh1)-mediated SENP2 degradation, leading to SENP2 nuclear accumulation.
  • SENP2 nuclear accumulation promotes MEF2A deSUMOylation and acetylation, resulting in transcriptional activation.
  • Cdh1's regulation of MEF2A transcriptional activity is dependent on SENP2.

Conclusions:

  • A novel post-transcriptional regulatory mechanism for MEF2A transcriptional activation is defined.
  • The APC(Cdh1)-SENP2-MEF2A axis is crucial for responding to activity-dependent stimuli.
  • This axis integrates ubiquitination, deSUMOylation, and acetylation to control MEF2A function.
Keywords:
APC-Cdh1MEF2ASENP2activity-dependent stimuli

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