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A recent report showed PINK1 transcript levels to be up- or down-regulated by the gain or loss of Ataxin-2 function, respectively, in human blood, in a human neural cell line and in mouse tissues. These observations may have profound implications for the regulation of cell growth and may be medically exploited for the treatment of cancer and neural atrophy...
A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.