RGD Reference Report - CREB SUMOylation by the E3 ligase PIAS1 enhances spatial memory. - Rat Genome Database

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CREB SUMOylation by the E3 ligase PIAS1 enhances spatial memory.

Authors: Chen, YC  Hsu, WL  Ma, YL  Tai, DJ  Lee, EH 
Citation: Chen YC, etal., J Neurosci. 2014 Jul 16;34(29):9574-89. doi: 10.1523/JNEUROSCI.4302-13.2014.
RGD ID: 10059390
Pubmed: PMID:25031400   (View Abstract at PubMed)
PMCID: PMC6608321   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.4302-13.2014   (Journal Full-text)

cAMP-responsive element binding protein (CREB) phosphorylation and signaling plays an important role in long-term memory formation, but other posttranslational modifications of CREB are less known. Here, we found that CREB1Delta, the short isoform of CREB, could be sumoylated by the small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) at Lys271 and Lys290 and PIAS1 SUMOylation of CREB1Delta increased the expression level of CREB1Delta. CREB1Delta could also be sumoylated by other PIAS family proteins, but not by the E3 ligases RanBP2 and Pc2 or by the E2 ligase Ubc9. Furthermore, water maze training increased the level of endogenous CREB SUMOylation in rat CA1 neurons determined by in vitro SUMOylation assay, but this effect was not observed in other brain areas. Moreover, transduction of Lenti-CREBWT to rat CA1 area facilitated, whereas transduction of Lenti-CREB double sumo-mutant (CREBK271RK290R) impaired, spatial learning and memory performance. Transduction of Lenti-CREBWT-SUMO1 fusion vector to rat CA1 area showed a more significant effect in enhancing spatial learning and memory and CREB SUMOylation. Lenti-CREBWT transduction increased, whereas Lenti-CREBK271RK290R transduction decreased, CREB DNA binding to the brain-derived neurotrophic factor (bdnf) promoter and decreased bdnf mRNA expression. Knock-down of PIAS1 expression in CA1 area by PIAS1 siRNA transfection impaired spatial learning and memory and decreased endogenous CREB SUMOylation. In addition, CREB SUMOylation was CREB phosphorylation dependent and lasted longer. Therefore, CREB phosphorylation may be responsible for signal transduction during the early phase of long-term memory formation, whereas CREB SUMOylation sustains long-term memory.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Pias1Ratpositive regulation of protein sumoylation  IMP  RGD 
Creb1Ratresponse to activity  IEP  RGD 
Creb1Ratvisual learning  IMP  RGD 
Pias1Ratvisual learning  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Creb1Ratprotein binding  IPIPias1 (Rattus norvegicus) RGD 
Pias1Ratprotein binding  IPICreb1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Creb1  (cAMP responsive element binding protein 1)
Pias1  (protein inhibitor of activated STAT, 1)


Additional Information