Nuclear receptor RXRα binds the precursor of miR-103 to inhibit its maturation.

Background: The maturation of microRNAs (miRNAs) successively undergoes Drosha, Dicer, and Argonaute -mediated processing, however, the intricate regulations of the individual miRNA maturation are largely unknown. Retinoid x receptor alpha (RXRα) belongs to nuclear receptors that regulate gene transcription by binding to DNA elements, however, whether RXRα binds to miRNAs to exert physiological functions is not known.

Results: In this work, we found that RXRα directly binds to the precursor of miR-103 (pre-miR-103a-2) via its DNA-binding domain with a preferred binding sequence of AGGUCA.

Design, synthesis and biological evaluation of acyl hydrazones-based derivatives as RXRα-targeted anti-mitotic agents.

RXRα, a unique and important nuclear receptor, plays a vital role in various biological and pathological pathways, including growth, differentiation, and apoptosis. We recently reported a transcription-independent function of RXRα in cancer cells in which RXRα is phosphorylated by Cdk1 at the onset of mitosis, resulting in its translocation to the centrosome, where the phosphorylated RXRα (p-RXRα) interacts with polo-like kinase 1 (PLK1) to promote centrosome maturation and mitotic progression. Significantly, we also identified that a small molecule XS-060 binds to RXRα and selectively inhibits the p-RXRα/PLK1 interaction to induce mitotic arrest and catastrophe in cancer cells.

Protocol to identify centrosome-associated transcription factors during mitosis in mammalian cell lines.

During eukaryotic cell mitosis, the nuclear envelope disintegrates and transcription factors are dissociated from condensed chromosomes. Here, we describe a protocol to study centrosomal translocation of nuclear receptor RXRα. We detail procedures for HeLa cell synchronization followed by immunofluorescence, in situ proximity ligation assay, and centrosome isolation.

Centrosomal Localization of RXRα Promotes PLK1 Activation and Mitotic Progression and Constitutes a Tumor Vulnerability.

Retinoid X receptor alpha (RXRα), a nuclear receptor of transcription factor, controls various physiological and pathological pathways including cellular growth, proliferation, differentiation, and apoptosis. Here, we report that RXRα is phosphorylated at its N-terminal A/B domain by cyclin-dependent kinase 1 (Cdk1) at the onset of mitosis, triggering its translocation to the centrosome, where phosphorylated-RXRα (p-RXRα) interacts with polo-like kinase 1 (PLK1) through its N-terminal A/B domain by a unique mechanism. The interaction promotes PLK1 activation, centrosome maturation, and mitotic progression.

TBMS1 exerts its cytotoxicity in NCI-H460 lung cancer cells through nucleolar stress-induced p53/MDM2-dependent mechanism, a quantitative proteomics study.

Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti-tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1.

Nitrostyrene Derivatives Act as RXRα Ligands to Inhibit TNFα Activation of NF-κB.

Retinoid X receptor alpha (RXRα) and its N-terminally truncated version, tRXRα, are widely implicated in cancer development and represent intriguing targets for cancer prevention and treatment. Successful manipulation of RXRα and tRXRα requires the identification of their modulators that could produce therapeutic effects. Here, we report that a class of nitrostyrene derivatives bind to RXRα by a unique mechanism, of which the nitro group of nitrostyrene derivatives and Cys432 of RXRα are required for binding.

Induction of Nur77-dependent apoptotic pathway by a coumarin derivative through activation of JNK and p38 MAPK.

Coumarins are plant-derived natural products with a broad range of known pharmacological activities including anticancer effects. However, the molecular mechanisms by which this class of promising compounds exerts their anticancer effects remain largely unknown. We report here that a furanocoumarin named apaensin could effectively induce apoptosis of cancer cells through its activation of Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK).

Characterization of antiproliferative activity constituents from Artocarpus heterophyllus.

Artocarpus heterophyllus is an evergreen fruit tree cultivated in many tropical regions. Previous studies have shown that some of its compositions exhibited potential tyrosinase inhibition activities. This study indentified 8 new phenolic compounds, artoheterophyllins E-J (1-6), 4-geranyl-2',3,4',5-tetrahydroxy-cis-stilbene (7), and 5-methoxymorican M (8) and 2 new natural compounds (9 and 10), 2,3-dihydro-5,7-dihydroxy-2-(2-hydroxy-4-methoxyphenyl)-4H-benzopyran-4-one and 6-[(1S,2S)-1,2-dihydroxy-3-methylbutyl]-2-(2,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-3-(3-methyl-2-buten-1-yl)-4H-1-benzopyran-4-one, together with 23 known compounds (11-33), from the ethanol extract of the wood of A.

Free energy profiles for monomer capture in Grubbs- and SHOP-type olefin polymerization catalysts: a constraint ab initio molecular dynamics study.

Density functional theory together with Car-Parrinello ab initio molecular dynamics simulation has been used to investigate the free energy profiles (FEP) of monomer capture in Grubbs- and SHOP-type olefin polymerization catalysts. The FEPs along the reaction coordinates at 300 K were determined directly by a point wise thermodynamic integration technique. Comparison between potential energy profile (PEP) and the FEP has been made.

Analysis of the effects of protic, aprotic, and multi-component solvents on the fluorescence emission of naphthalene and its exciplex with triethylamine.

The emission spectra of naphthalene (NP)-triethylamine (TEA) systems were measured under steady-state illumination conditions in some protic and aprotic solvent-tetrahydrofuran (THF) mixtures. The fluorescence spectrum of the NP-TEA system in THF could be separated into two component bands (band A at 329 nm (fluorescence of NP) and band B at 468 nm (emission from an intermolecular exciplex)). The intensities of bands A and B decreased with increasing solvent polarity.