Bromodomain-containing 4(BRD4)has been considered as an important requirement for disease maintenance and an attractive therapeutic target for cancer therapy.This protein can be targeted by JQ1,a selective small-molecule inhibitor.However,few studies have investigated whether BRD4influenced acute promyelocytic leukemia (APL),and whether BRD4had interaction with promyelocytic leukemia-retinoic acid receptor a (PML/RARa)fusion protein to some extent.Results from cell viability assay,cell cycle analysis,and Annexin-V/PI analysis indicated that JQ1inhibited the growth of NB4cells,an APL-derived cell line,and induced NB4cell cycle arrest at G1and apoptosis.Then,we used co-immunoprecipitation (co-IP)assay and immunoblot to demonstrate the endogenous interaction of BRD4and PML/RARa in NB4cells.Moreover,downregulation of PML/RARa at the mRNA and protein levels was observed upon JQ1treatment.Furthermore,results from the RT-qPCR,ChIP-qPCR,and re-ChIP-qPCR assays showed that BRD4and PML/RARu co-existed on the same regulatory regions of their target genes.Hence,we showed a new discovery of the interaction of BRD4and PML/ RARa,as well as the decline of PML/RARa expression,under JQ1treatment.
Laccase is a promising oxidase with environmental applications, such as lignin degradation and chlorophenol detoxification. Laccase immobilization can significantly improve physiochemical stability and reusability compared to the free enzymes. In this work, anion effect was investigated in entrapment of Cu-alginate matrix with five types of anions, including perchlorate(ClO4à), nitrate(NO3à), sulfate(SO42à), chloride(Clà), and acetate(CH3CO2à). Accordingly, chloride inhibition and acetate activation were detected in the o-tolidine kinetic experiments, while effects of the other three anions were much smaller. Such counteranion effects were also observed in the laccase-catalyzed biodegradation of 2,4-dichlorophenol. The results indicated that counteranions in the enzyme immobilization process are crucial for catalytic capacity, probably due to the competition with the carboxylate groups in alginate.Our results also imply that these anions might coordinate the copper cations in laccase.
