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Genome instability is a common feature of tumor cells, and the persistent presence of genome instability is a potential mechanism of tumorigenesis. The E3 ubiquitin ligase MDM2 is intimately involved in genome instability, but its mechanisms are unclear. Our data demonstrated that the transcription factor HBP1 is a target of MDM2. MDM2 facilitates HBP1 proteasomal degradation by ubiquitinating HBP1, regardless of p53 status, thus attenuating the transcriptional inhibition of HBP1 in the expression of its target genes, such as the DNA methyltransferase DNMT1 and histone methyltransferase EZH2, which results in global DNA hypermethylation and histone hypermethylation and ultimately genome instability. The repression of HBP1 by MDM2 finally promotes cell growth and tumorigenesis. Next, we thoroughly explored the regulatory mechanism of the MDM2/HBP1 axis in DNA damage repair following ionizing radiation. Our data indicated that MDM2 overexpression-mediated repression of HBP1 delays DNA damage repair and causes cell death in a p53-independent manner. This investigation elucidated the mechanism of how MDM2 promotes genome instability and enhances tumorigenesis in the absence of p53, thus providing a theoretical and experimental basis for targeting MDM2 as a cancer therapy.

We demonstrate direct measurements of the spin-orbit interaction and Landé g factors in a semiconductor nanowire double quantum dot. The device is made from a single-crystal purephase InAs nanowire on top of an array of finger gates on a Si/SiO2 substrate and the measurements are performed in the Pauli spin-blockade regime. It is found that the double quantum dot exhibits a large singlet-triplet energy splitting of ΔST ~2.3 meV, a strong spinorbit interaction of ΔSO ~140 eV, and a large and strongly level-dependent Landé g factor of ~12.5. These results imply that single-crystal pure-phase InAs nanowires are desired semiconductor nanostructures for applications in quantum information technologies.

Background Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway. Methods Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting. Results Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis. Conclusion Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

Understanding of the Schottky barriers formed at metal contact-InAs nanowire interfaces is of great importance for the development of high-performance InAs nanowire nanoelectronic and quantum devices. Here, we report a systematical study of InAs nanowire field-effect transistors (FETs) and the Schottky barrier heights formed at the contact-nanowire interfaces. The InAs nanowires employed are grown by molecular beam epitaxy and are high material quality single crystals, and the devices are made by directly contacting the nanowires with a series of metals of different work functions. The fabricated InAs nanowire FET devices are characterized by electrical measurements at different temperatures and the Schottky barrier heights are extracted from the measured temperature and gate-voltage dependences of the channel current. We show that although the work functions of the contact metals are widely spread, the Schottky barrier heights are determined to be distributed over 35–55 meV, showing a weak but not negligible dependence on the metals. The deduced Fermi level in the InAs nanowire channels is found to be in the band gap and very close to the conduction band. The physical origin of the results is discussed in terms of Fermi level pinning by the surface states of the InAs nanowires and a shift in pinned Fermi level induced by the metal-related interface states.