Abstract The structural, functional, and mechanistic characterization of several types post‐translational modifications (PTMs) is well‐documented. PTMs, however, may interact or interfere with one another when regulating protein function. Yet, the structural functional signatures their crosstalk has been hindered by scarcity data. To this end, we developed a unified sequence‐based predictor 23 PTM sites that, believe, useful tool in guiding biological experiments data interpretation. We then...

Molecular recognition features (MoRFs) are intrinsically disordered protein regions that bind to partners via disorder-to-order transitions. In one-to-many binding, a single MoRF binds two or more different individually. MoRF-based protein-protein interaction (PPI) examples were collected from the Protein Data Bank, yielding 23 MoRFs bound 2-9 partners, with all pairs of same-MoRF having less than 25% sequence identity. Of these, 8 completely folds, whereas 15 2-5 same folds but low...

Amyloid-β (Aβ) oligomers largely initiate the cascade underlying pathology of Alzheimer's disease (AD). Galectin-3 (Gal-3), which is a member galectin protein family, promotes inflammatory responses and enhances homotypic aggregation cancer cells. Here, we examined role action mechanism Gal-3 in Aβ oligomerization toxicities. Wild-type (WT) Gal-3-knockout (KO) mice, APP/PS1;WT APP/PS1;Gal-3+/− mice brain tissues from normal subjects AD patients were used. We found that reduced KO injected...

Abstract The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2 , is an X-linked gene encoding the MeCP2 protein, and mutations of cause Rett syndrome (RTT). However, molecular mechanism ME CP2 -mutation-caused RTT less known. Here we find that could be SUMO-modified by E3 ligase PIAS1 at Lys-412. phosphorylation (at Ser-421 Thr-308) facilitates SUMOylation, SUMOylation induced NMDA, IGF-1 CRF in rat brain. releases CREB from repressor complex enhances Bdnf mRNA expression. Several identified...

By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are expressed differentially between fast learners and slow in water maze learning task. One of these encodes serum- glucocorticoid-inducible kinase ( sgk ) gene. Northern blot analysis revealed mRNA level was approximately 4-fold higher than learners. In situ hybridization results indicated increased markedly CA1, CA3, dentate gyrus Transient transfection mutant DNA to CA1 area...

Abstract We have previously demonstrated that the serum and glucocorticoid‐inducible kinase ( sgk ) gene plays a causal role in facilitating memory performance rats. Environment enrichment is known to facilitate spatial learning. therefore examined effect of on expression. also nonspatial learning regulation expression by activation different glutamate receptors. Both real‐time polymerase chain reaction Western blot analyses revealed training preferentially increased mRNA protein levels...

Amyloid-β (Aβ) produces neurotoxicity in the brain and causes neuronal death, but endogenous defense mechanism that is activated on Aβ insult less well known. Here we found acute increases expression of PIAS1 Mcl-1 via activation MAPK/ERK, induction enhances HDAC1 SUMOylation rat hippocampus. Knockdown decreases blocks Mcl-1. Sumoylated reduces it association with CREB, CREB binding to promoter mediates expression. Transduction SUMO-modified lenti-HDAC1 vector hippocampus APP/PS1 mice...

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 CREB1Δ, the short isoform CREB, could be sumoylated by small ubiquitin-like modifier (SUMO) E3 ligase inhibitor activated STAT1 (PIAS1) at Lys271 Lys290 PIAS1 SUMOylation CREB1Δ increased expression level CREB1Δ. also PIAS family proteins, not ligases RanBP2 Pc2 or E2 Ubc9....

Signal transducer and activator of transcription-1 (STAT1) has an important role in inflammation the innate immune response, but its central nervous system is less well understood. Here, we examined STAT1 spatial learning memory, assessed involvement mediating memory-impairing effect amyloid-beta (Aβ). We found that water maze training downregulated expression rat hippocampal CA1 area, memory function was enhanced Stat1-knockout mice. Conversely, overexpression impaired performance. strongly...

The amyloid precursor protein (APP) intracellular domain (AICD) is implicated in the pathogenesis of Alzheimer's disease (AD), but post-translational modification AICD has rarely been studied and its role AD unknown. In this study, we examined molecular mechanism SUMOylation AD. We found that SUMO-modified by SUMO E3 ligase inhibitor activated STAT1 (PIAS1) hippocampus at Lys-43 predominantly, knockdown PIAS1 decreases endogenous SUMOylation. increases association with binding Fe65 nuclear...

Previous studies showed that the serum- and glucocorticoid-inducible kinase ( sgk ) gene plays an important role in long-term memory formation. The present study further examined of SGK potentiation (LTP). dominant-negative mutant sgk, SGKS422A, was used to inactivate SGK. Results revealed a time-dependent increase phosphorylation after tetanization with significant effect observed 3 h 5 later. Transfection SGKS422A impaired expression, but not induction, LTP. Furthermore, constitutively...

Abstract The methyl-CpG-binding protein 2 gene, MECP2 , is an X chromosome-linked gene encoding the MeCP2 protein, and mutations of cause Rett syndrome (RTT). Previous study has shown that re-expression SUMO-modified in Mecp2 -null neurons rescues synaptic behavioral deficits conditional knockout mice, whereas about 12-fold decrease Wnt6 mRNA level was found MeCP2K412R sumo-mutant mice. Here, we examined role T158A mouse model RTT. Results show lentiviral delivery to amygdala ameliorates...

Although estrogen is recognized as essential for embryonic development and maintenance of pregnancy, it remains unclear whether has a direct role in the embryos themselves. The aim this study was to investigate can have any effect pig during preimplantation development. Since function mediated through its specific receptor, receptor (ER), presence ER mRNA protein collected vivo at different stages determined compared. Using reverse transcription polymerase chain reaction, RNA detected...

Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in adult rat hippocampus, but its role learning memory function not known. Here, we that contextual fear-conditioning training, spatial training or injection NMDA into CA1 area each dramatically decreased level endogenous galectin-3 expression. Overexpression impaired fear memory, whereas knockout (KO) enhanced...

Background and Purpose Protein inhibitor of activated STAT1 (PIAS1) is phosphorylated by IKKα at Ser 90 in a PIAS1 E3 ligase activity‐dependent manner. Whether also other residues the functional significance these additional phosphorylation events are not known. The transcription factor Elk‐1 remains SUMOylated under basal conditions, but role SUMOylation brain unknown. Here, we examined PIAS1‐mediated Alzheimer's disease (AD) using APP/PS1 mouse model AD amyloid β (Aβ) microinjections vivo....

OBJECTIVE: It is not known whether progesterone, which plays a key role in establishing and maintaining pregnancy, acts directly on embryos or indirectly through the mother's reproductive tract. Since physiological effects of progesterone are mediated by receptors (PR), expression PR during preimplantation stages pig was determined. DESIGN AND METHODS: Preimplantation at different developmental were examined using reverse transcription-polymerase chain reaction techniques for purpose...

Smad4 is a critical effector of TGF-β signaling that regulates variety cellular functions. However, its role in the brain has rarely been studied. Here, we examined molecular mechanisms underlying post-translational regulation function by SUMOylation, and spatial memory formation. In hippocampus, SUMOylated E3 ligase PIAS1 at Lys-113 Lys-159. Both training NMDA injection enhanced SUMOylation. Inhibition SUMOylation impaired learning rats downregulating TPM2, gene associated with skeletal...

Disorder prediction for short peptides is important and difficult. All modern predictors have to be optimized on a preselected dataset prior prediction. In the succeeding process, predictor works query sequence or its segment. For implementing smoothly obtaining sound results, specific length of segment usually required. The need in optimization process limitation restrict predictors' performance. To minimize influence these limitations, we developed method intrinsic disorder based large...

Although estrogen is recognized as essential for embryonic development and maintenance of pregnancy, it remains unclear whether has a direct role in the embryos themselves. The aim this study was to investigate can have any effect pig during preimplantation development. Since function mediated through its specific receptor, receptor (ER), presence ER mRNA protein collected vivo at different stages determined compared. Using reverse transcription polymerase chain reaction, RNA detected...

We have previously found that the protein inhibitor of activated STAT1 ( pias1 ) gene is differentially expressed between fast learners and slow from water maze learning task with showing a higher expression level in hippocampal neurons. Spatial training also increases PIAS1 rat CA1 area. Further, overexpression neurons enhances whereas knockdown impairs spatial memory performance rats. Because transcriptional regulator possesses small ubiquitin‐like modifier (SUMO) E3 ligase activity, this...