PMID- 25031400 OWN - NLM STAT- MEDLINE DCOM- 20140905 LR - 20231213 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 34 IP - 29 DP - 2014 Jul 16 TI - CREB SUMOylation by the E3 ligase PIAS1 enhances spatial memory. PG - 9574-89 LID - 10.1523/JNEUROSCI.4302-13.2014 [doi] AB - 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. CI - Copyright (c) 2014 the authors 0270-6474/14/349574-16$15.00/0. FAU - Chen, Yan-Chu AU - Chen YC AD - Graduate Institute of Life Sciences, National Defense Medical Center, and. FAU - Hsu, Wei-Lun AU - Hsu WL AD - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China. FAU - Ma, Yun-Li AU - Ma YL AD - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China. FAU - Tai, Derek J C AU - Tai DJ AD - Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China. FAU - Lee, Eminy H Y AU - Lee EH AD - Graduate Institute of Life Sciences, National Defense Medical Center, and Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China eminy@gate.sinica.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Protein Inhibitors of Activated STAT) RN - 0 (Protein Isoforms) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cyclic AMP Response Element-Binding Protein/genetics/*metabolism MH - Gene Expression Regulation/drug effects/genetics MH - Green Fluorescent Proteins/genetics/metabolism MH - HEK293 Cells MH - Hippocampus/metabolism MH - Humans MH - Male MH - Maze Learning/drug effects/physiology MH - Memory/drug effects/*physiology MH - Protein Binding/genetics MH - Protein Inhibitors of Activated STAT/genetics/*metabolism MH - Protein Isoforms/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/genetics MH - Space Perception/*physiology MH - Sumoylation/drug effects/genetics/*physiology MH - Time Factors PMC - PMC6608321 OTO - NOTNLM OT - CREB OT - PIAS1 OT - SUMOylation OT - phosphorylation OT - spatial learning and memory EDAT- 2014/07/18 06:00 MHDA- 2014/09/06 06:00 PMCR- 2015/01/16 CRDT- 2014/07/18 06:00 PHST- 2014/07/18 06:00 [entrez] PHST- 2014/07/18 06:00 [pubmed] PHST- 2014/09/06 06:00 [medline] PHST- 2015/01/16 00:00 [pmc-release] AID - 34/29/9574 [pii] AID - 4302-13 [pii] AID - 10.1523/JNEUROSCI.4302-13.2014 [doi] PST - ppublish SO - J Neurosci. 2014 Jul 16;34(29):9574-89. doi: 10.1523/JNEUROSCI.4302-13.2014.