The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for ubiquitination and degradation
Copyright policy )The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for ubiquitination and degradation
Activity-dependent stimuli induced a calcineurin-mediated dephosphorylation of the transcriptional factor MEF2A at serine408 and promoted a switch from SUMOylation to acetylation at lysine403 which led to MEF2A transcriptional activation. We previously identified SENP2 is the de-SUMOylation enzyme for MEF2A and promotes MEF2A-dependent transcription. We report here a requirement for APC(Cdh1)-SENP2-MEF2A axis in the regulation of MEF2A transcriptional activation. APC(Cdh1) interacts with and targets SENP2 for ubiquitination and destruction in the cytoplasm by recognizing a conserved canonical D-box motif in SENP2. Moreover, Cdh1 regulates the transcriptional activity of MEF2A in a SENP2 dependent manner. Activity-dependent stimuli prevented APC(Cdh1)-induced SENP2 ubiquitination, promoted SENP2 nuclear accumulations, and caused MEF2A de-SUMOylation and MEF2A acetylation, leading to MEF2A transcriptional activation. Thus, our findings defined a post-transcriptional mechanism underlying activity-dependent stimuli-induced MEF2A transcriptional activation.
- Shanghai Jiao Tong University China (People's Republic of)
- Shanghai Institute of Materia Medica China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
- Hubei Polytechnic University China (People's Republic of)
- Shanghai University China (People's Republic of)
Transcriptional Activation, MEF2 Transcription Factors, Amino Acid Motifs, Ubiquitination, Sumoylation, Cadherins, Anaphase-Promoting Complex-Cyclosome, Potassium Chloride, Cysteine Endopeptidases, Antigens, CD, Cell Line, Tumor, Humans, RNA Interference, RNA, Small Interfering
Transcriptional Activation, MEF2 Transcription Factors, Amino Acid Motifs, Ubiquitination, Sumoylation, Cadherins, Anaphase-Promoting Complex-Cyclosome, Potassium Chloride, Cysteine Endopeptidases, Antigens, CD, Cell Line, Tumor, Humans, RNA Interference, RNA, Small Interfering
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