Activator protein 1 (AP-1) is a transcriptional factor composed of the dimeric members of bZIP proteins, which are frequently deregulated in human cancer cells. In this study, we aimed to identify an oncogenic AP-1 dimer critical for the proliferation of neuroblastoma cells and to investigate whether histone deacetylase inhibitors (HDACIs), a new generation of anticancer agents, could target the AP-1 dimer. We report here that HDACIs including trichostatin A, suberoylanilidehydroxamic acid, valproic acid and M344 can transcriptionally suppress both c-Jun and Fra-1, preceding their inhibition of cell growth. c-Jun preferentially interacting with Fra-1 as a heterodimer is responsible for AP-1 activity and critical for cell growth. Mechanistically, HDACIs suppress Fra-1 expression through transcriptionally downregulating Raf1 and subsequently decreasing MEK1/2-ERK1/2 activity. Unexpectedly, HDACI treatment caused MKK7 downregulation at both the protein and mRNA levels. Deletion analysis of the 5′-flanking sequence of the MKK7 gene revealed that a major element responsible for the downregulation by HDACI is located at −149 to −3 relative to the transcriptional start site. Knockdown of MKK7 but not MKK4 remarkably decreased JNK/c-Jun activity and proliferation, whereas ectopic MKK7-JNK1 reversed HDACI-induced c-Jun suppression. Furthermore, suppression of both MKK-7/c-Jun and Raf-1/Fra-1 activities was involved in the tumor growth inhibitory effects induced by SAHA in SH-SY5Y xenograft mice. Collectively, these findings demonstrated that c-Jun/Fra-1 dimer is critical for neuroblastoma cell growth and that HDACIs act as effective suppressors of the two oncogenes through transcriptionally downregulating MKK7 and Raf1.

A DXR gene, AvDXR (GenBank accession no. FJ459894), and a DXS gene, AvDXS (GenBank accession no. FJ455512), were isolated from the leaves of Amomum villosum, one of the most well-known and authentic herbs in South China. The 1,749-bp full-length cDNA of AvDXR encoded a peptide of 472 amino acids, and the 2,347-bp full-length cDNA of AvDXS encoded a peptide of 715 amino acids. The deduced amino acid sequences of the AvDXR and AvDXS proteins share high homology with DXRs and DXSs from other plant species, and AvDXS belongs to class 1 plant DXS. The characterization based on bioinformatic analysis indicated that the AvDXR and AvDXS encoded functional proteins as DXR and DXS, respectively. The functional color assay in Escherichia coli with pAC-BETA implied that AvDXR and AvDXS encoded functional proteins that manipulated the biosynthesis of isoprenoid precursors. Both AvDXR and AvDXS were expressed extensively in the leaves, stems, roots, pericarps and seeds of A. villosum. AvDXS expression was similar in all tissues investigated, whereas higher levels of AvDXR were observed in the fruits, the main part for the accumulation of volatile oil in this plant. AvDXR was transformed into tobacco to confirm its function further. Overexpression of AvDXR in transgenic T1 generation tobacco increased DXR activity, photosynthetic pigment content and volatile isoprenoid components, and the increase of photosynthetic pigment content was consistent with the AvDXR transcription level. This study demonstrated that AvDXR plays important role in isoprenoid biosynthesis and it is useful for metabolic engineering.

Within a decade, black phosphorus has become an important 2D material for sustainable energy areas and bioapplications due to its great electronic properties and biocompatibility. Pristine black phosphorus suffers from intrinsic shortages like rapid degradation and poor solubility, which require physical and chemical tuning methods. There also lacks an effective approach to synthesize single-crystal black phosphorus with large areas. This review article provides a forward-looking overview of significance, mechanism studies, status quo, and outlooks of defect-tailoring and surface functionalization in black phosphorus; the prior focuses on the lattice while the latter focuses on the surface. Particularly, both approaches can alter chemical and electronic properties such as air stability, solubility, carrier mobility, and band gap. Functionalization further enables the BP surface to immobilize various biomarkers and medical molecules, which largely boost its future applications in biosensors and theranotics. Finally, we discuss some unresolved issues and future applications, especially in tuning BP especially in BP synthesis, atomic modification methods, and bioapplications.