Summary DUSP6 functions as an important negative feedback component of the MAPK/ERK signaling pathway. Although DUSP6 expression is tightly regulated by ERK1/2 signaling, the molecular mechanism of this regulation remains partially understood. In this work, we show that the transcriptional repressor CIC functions downstream of the ERK1/2 signaling to negatively regulate DUSP6 expression. CIC directly represses DUSP6 transcription by binding to three cis -regulatory elements (CREs) in DUSP6 promoter. p90RSK, a downstream target of ERK1/2, phosphorylates CIC at S173 and S301 sites, which creates a 14-3-3 recognition motif, resulting in 14-3-3-mediated nuclear export of CIC and derepression of DUSP6. Finally, we demonstrate that the oncogenic CIC-DUX4 fusion protein acts as a transcriptional activator of DUSP6 and its nuclear/cytoplasmic distribution remains regulated by ERK1/2 signaling. These results complete an ERK1/2/p90RSK/CIC/DUSP6 negative feedback circuit and elucidate the molecular mechanism of how RTK/MAPK signaling harnesses the transcriptional repressor activity of CIC in mammalian cells.

No abstract

Background Gold nanoparticles (AuNPs) have been proposed for many applications in medicine and bioanalysis. For use in all these applications, maintaining the stability of AuNPs in solution by suppressing aggregation is paramount. Herein, the effects of amino acids were investigated in stabilizing AuNPs by rationally designed peptide scaffolds. Results Compared to other tested amino acids, phosphotyrosine (pY) significantly stabilized AuNPs. Our results indicated that pY modified AuNPs presented a high level of stability in various solutions, and had good biocompatibility. When a pY-peptide was used in stabilizing AuNPs, the phosphate group could be removed by phosphatases, which subsequently caused the aggregation and the cargo release of AuNPs. In vitro study showed that AuNPs formed aggregation in a phosphatase concentration depending manner. The aggregation of AuNPs was well correlated with the enzymatic activity (R 2 = 0.994). In many types of cancer, a significant increase in phosphatases has been observed. Herein, we demonstrated that cancer cells treated with pY modified AuNPs in conjunction with doxorubicin killed SGC-7901 cells with high efficiency, indicating that the pY peptide stabilized AuNPs could be used as carriers for targeted drug delivery. Conclusion In summary, pY peptides can act to stabilize AuNPs in various solutions. In addition, the aggregation of pY-AuNPs could be tuned by phosphatase. These results provide a basis for pY-AuNPs acting as potential drug carriers and anticancer efficacy. Electronic supplementary material The online version of this article (10.1186/s12951-019-0522-y) contains supplementary material, which is available to authorized users.

No abstract

Both reduced and oxidized forms of glutathiones were firstly stacked and detected using pH-mediated acid stacking method, in which glutathiones were stacked as cations and separated as anions. Factors, such as injection time, sweeping time, buffer pH, concentration of sodium chloride in sample matrix, that influenced stacking and separation were systematically studied and optimized. Under the optimum condition, the enhancement factors of ~20 times for both reduced and oxidized forms of glutathiones could be easily obtained within 20 min with satisfied sensitivities (limit of detections were 0.12 and 0.06 μmol/L for reduced and oxidized glutathione, respectively, at signal-to-noise ratio, S/N = 3), linearity range (0.3-300.0 and 0.6-300.0 μmol/L for reduced and oxidized glutathione, respectively), recoveries (>98%) and reproducibilities (relative standard deviation <5.1% for peak height). The proposed method provides an alternation way for assaying of glutathiones, as well as amphoteric compounds, in blood sample.