title: The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for ubiquitination and degradation.
abstract: 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.
authors.affiliation: a Department of Anesthesiology ; Ruijin Hospital ; Shanghai Jiao-Tong University School of Medicine (SJTU-SM) ; Shanghai , People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Qu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Bu-Wei
authors.initials: BW
authors.lastname: Yu
mesh_terms: D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D015703:Antigens, CD; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D058207:Sumoylation; D015533:Transcriptional Activation / Q000187:drug effects; D054875:Ubiquitination
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064326:MEF2 Transcription Factors; D034741:RNA, Small Interfering; D011189:Potassium Chloride; D064173:Anaphase-Promoting Complex-Cyclosome; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human
keywords: APC-Cdh1; MEF2A; SENP2; activity-dependent stimuli