Targeted inactivation of Runx3 in mouse lung induced mucinous and nonmucinous adenomas and markedly shortened latency of adenocarcinoma formation induced by oncogenic K-Ras. RUNX3 was frequently inactivated in K-RAS mutated human lung adenocarcinomas. A functional genetic screen of a fly mutant library and molecular analysis in cultured cell lines revealed that Runx3 forms a complex with BRD2 in a K-Ras-dependent manner in the early phase of the cell cycle; this complex induces expression of p14(ARF)/p19(Arf) and p21(WAF/CIP). When K-Ras was constitutively activated, the Runx3-BRD2 complex was stably maintained and expression of both p14(ARF) and p21(WAF/CIP) was prolonged. These results provide a missing link between oncogenic K-Ras and the p14(ARF)-p53 pathway, and may explain how cells defend against oncogenic K-Ras.

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The cellular decision regarding whether to undergo proliferation or death is made at the restriction (R)-point, which is disrupted in nearly all tumors. The identity of the molecular mechanisms that govern the R-point decision is one of the fundamental issues in cell biology. We found that early after mitogenic stimulation, RUNX3 binds to its target loci, where it opens chromatin structure by sequential recruitment of Trithorax group proteins and cell-cycle regulators to drive cells to the R-point. Soon after, RUNX3 closes these loci by recruiting Polycomb repressor complexes, causing the cell to pass through the R-point toward S phase. If the RAS signal is constitutively activated, RUNX3 inhibits cell cycle progression by maintaining R-point-associated genes in an open structure. Our results identify RUNX3 as a pioneer factor for the R-point and reveal the molecular mechanisms by which appropriate chromatin modifiers are selectively recruited to target loci for appropriate R-point decisions.

While active materials based on germanium (Ge) are considered as a promising alternative anodic electrode due to their relatively high reversible capacity and excellent lithium-ion diffusivity, the quite unstable structural/electrochemical stability and severe volume expansion or pulverization problems of Ge electrodes remain a considerable challenge in lithium ion batteries (LIBs). Here, we present the development of Ge embedded in one-dimensional carbon nanostructures (Ge/CNs) synthesized by the modified in situ electrospinning technique using a mixed electrospun solution consisting of a Ge precursor as an active material source and polyacrylonitrile (PAN) as a carbon source. The as-prepared Ge/CNs exhibit superior lithium ion behavior properties, i.e., highly reversible specific capacity, rate performance, Li ion diffusion coefficient, and superior cyclic stability (capacity retention: 85% at 200 mA g(-1)) during Li alloying/dealloying processes. These properties are due to the high electrical conductivity and unique structures containing well-embedded Ge nanoparticles (NPs) and a one-dimensional carbon nanostructure as a buffer medium, which is related to the volume expansion of Ge NPs. Thus, it is expected that the Ge/CNs can be utilized as a promising alternative anodic material in LIBs.

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