Project description:VIC-1911, formerly known as TAS-119, is a next-generation, ATP-competitive AURKA inhibitor with high selectivity over AURKB and AURKC. In this study, we demonstrate that VIC-1911 potently and selectively inhibits AURKA signaling in diverse prostate cancer (PC) cell models, including both androgen receptor (AR)-positive and AR-negative cell lines. VIC-1911 treatment suppressed AURKA phosphorylation and downstream effectors at nanomolar concentrations without affecting AURKB/C activity, resulting in mitotic defects, DNA double-strand breaks (DSBs), and apoptosis. Transcriptomic profiling and immunofluorescence analysis revealed robust activation of DNA damage response pathways and the p53 pathway, consistent with mitotic catastrophe-induced genotoxic stress. Functionally, VIC-1911 significantly inhibited PC cell proliferation and tumor growth in xenograft models, including castration-resistant and AR-negative tumors. Given its ability to induce DNA damage, we evaluated the combinatorial effect of VIC-1911 with PARP inhibitors (PARPi). The combination exhibited synergistic anti-tumor effects in vitro and in vivo, leading to enhanced mitotic abnormalities, γH2AX accumulation, and cleaved PARP expression, even in homologous recombination (HR)-proficient settings. Importantly, VIC-1911 monotherapy and its combination with PARPi were well tolerated in vivo. These findings position VIC-1911 as a promising therapeutic agent for advanced prostate cancer, either as monotherapy or in combination with PARPi to broaden clinical efficacy beyond HR-deficient tumors
Project description:The coordination of chloroplast and nuclear genome status are critical for plant cell function, but the mechanism remain largely unclear. In this study, we report that Arabidopsis thaliana CHLOROPLAST AND NUCLEUS DUAL-LOCALIZED PROTEIN 1 (CND1) maintains genome stability in both the chloroplast and the nucleus.
2022-12-13 | GSE220489 | GEO
Project description:The complete chloroplast genome of Abeliophyllum distichum f. lilacinum Nakai (Oleaceae)
Project description:The regulator for chloroplast biogenesis (rcb) mutant was identified as a mutant defective in phytochrome-mediated chloroplast biogenesis. The rcb mutant has long hypocotyl and albino phenotypes. RCB initiates chloroplast biogenesis in the nucleus by promoting the degradation of the master repressors for chloroplast biogenesis, the PIFs (Phytochrome Interacting Factors). To understand how RCB regulates the expression of PIF-regulated genes, we performed genome-wide expression analysis of RCB-dependent genes using a rcb-10 null allele.