BET proteins inhibitor JQ-1 impaired the extinction of remote auditory fear memory: An effect mediated by insulinlikegrowthfactor2
by Kayla
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Fear extinction is an important preclinical model for behavioral therapy on human anxiety disorders, such as post-traumatic stress disorder (PTSD). Histone acetylation are involved in the extinction of fear memory. As a “reader” histone acetylation markers, role and domain bromodomain extraterminal (BET) protein in fear extinction remains unclear. In this study, we find that the emphasis BET proteins using small molecules JQ-1 has no effect on the acquisition of auditory fear or the fear of extinction recent hearing, but hearing the fear extinction interference distance.
We found that insulin-like growth factor 2 (IGF-2) mRNA and protein were up-regulated in the anterior cingulate cortex (ACC) after the fear memory extinction remote training, and that this effect is inhibited by JQ-1 administration. Furthermore, local delivery of the IGF-2 protein to save the ACC region remote memory extinction disruption caused by JQ-1 administration, which indicates IGF-2 mediates the effect on extinction JQ-1 remote memory.
Gene expression analysis showed that the JQ-1 treatment inhibits up-regulated expression of a key set of genes related to neuroplasticity following remote memory extinction profiles. Together, these findings establish BET as a mediator of epigenetic proteins for remote fear memory extinction. In particular, the findings of this study suggest that a preclinical cancer drug candidate, JQ-1 (or more BET bromodomain inhibitors) should be amended to prevent it from crossing the blood brain barrier and cause neurological side effects.
BET proteins inhibitor JQ-1 impaired the extinction of remote auditory fear memory: An effect mediated by insulinlikegrowthfactor2
Insulin – As Growth Factor two mRNA-Binding Protein 3 modulate the aggressiveness of Ewing sarcomas by CD164-CXCR4 Axis Set Ewing sarcoma (EWS) is the second most common bone and soft-tissue malignancy associated in children and young adults.
It is driven by the fusion oncogene EWS / FLI1 and is characterized by rapid growth and early metastasis. We have previously found that the mRNA binding protein IGF2BP3 is an important biomarker for EWS as IGF2BP3 high expression in primary tumors predicts poor prognosis of patients with EWS. We also show that IGF2BP3 improve anchorage-independent growth and cell migration EWS indicates that IGF2BP3 may work as a driver and molecular predictors of the development of EWS.
The purpose of this study was to further define IGF2BP3 role in the development of EWS. We show that high levels of mRNA expression correlated with EWS IGF2BP3 metastasis and disease progression in well-characterized tumor specimens EWS. EWS tumors with high levels of IGF2BP3 marked with the signature of a particular gene is enriched in chemokine-mediated signaling pathways. We also found that IGF2BP3 regulated CXCR4 expression via CD164. Significantly, CD164 and CXCR4 colocalized at the cell plasma membrane EWS on CXCL12 stimulation.
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human. This antibody is Unconjugated. Tested in the following application: WB, ELISA;WB:1/500-1/2000.ELISA:1/20000
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;ELISA:1:1000-1:2000, WB:1:200-1:1000, IHC:1:50-1:200
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human, Mouse. This antibody is Unconjugated. Tested in the following application: IHC, IF, ELISA;IHC:1/100-1/300.IF:1/200-1/1000.ELISA:1/5000
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: IHC, IF, ELISA;IHC:1/100-1/300.IF:1/200-1/1000.ELISA:1/20000
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IHC, IF; Recommended dilution: IHC:1:20-1:200, IF:1:20-1:200
Description: A polyclonal antibody against IGF2R. Recognizes IGF2R from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, IHC;ELISA:1:2000-1:5000, IHC:1:50-1:200
Description: This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate, although the binding sites for either are located on different segments of the receptor. This receptor functions in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. While the related mouse gene shows exclusive expression from the maternal allele, imprinting of the human gene appears to be polymorphic, with only a minority of individuals showing expression from the maternal allele.
Description: This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate, although the binding sites for either are located on different segments of the receptor. This receptor functions in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. While the related mouse gene shows exclusive expression from the maternal allele, imprinting of the human gene appears to be polymorphic, with only a minority of individuals showing expression from the maternal allele.
Description: This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate, although the binding sites for either are located on different segments of the receptor. This receptor functions in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. While the related mouse gene shows exclusive expression from the maternal allele, imprinting of the human gene appears to be polymorphic, with only a minority of individuals showing expression from the maternal allele.
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We further showed that the expression level IGF2BP3, CD164, and CXCR4 correlated in clinical samples and IGF2BP3 that / CD164 / CXCR4 signaling pathway promoted EWS cell motility in response to CXCL12 and under hypoxic conditions. Data presented are identified CD164 and CXCR4 as a novel functional IGF2BP3 downstream effectors showed that IGF2BP3 / CD164 / CXCR4 axis oncogenic may work as critical modulators EWS aggressiveness. In addition, expression levels IGF2BP3, CD164, and CXCR4 could be a novel predictive biomarker panel EWS development.
